Section 1: Epidemiology and aetiology
Leprosy is a chronic granulomatous infection affecting mainly the skin and peripheral nerves. It is caused by the bacteria Mycobacterium leprae. It is still endemic in many regions of the world. Despite the WHO's efforts, its incidence has not declined; 250,000 new cases are diagnosed each year and it is estimated that a further one million cases go undiagnosed.
In addition, even after completion of antibiotic treatment, when patients may be deemed 'cured' because they are no longer infectious, leprosy remains associated with long-term complications. These complications need to be promptly recognised and aggressively managed to prevent serious sequelae.1
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The mode of transmission of leprosy is not well understood but is probably from person to person by nasal droplets. Leprosy is not highly contagious and for people to be at risk of infection they require close long-term contact with infected individuals with untreated leprosy. This may be because M leprae is non-viable in the environment. Tourists or short-term travellers to endemic regions are usually not at risk.
New cases of leprosy in the UK are more likely to be encountered in immigrants or returning nationals who have lived and worked in endemic regions. This includes missionaries, healthcare workers and those who regularly visit relatives abroad. Children are also susceptible. Highly endemic regions include south Asia, Indonesia, Brazil, Ethiopia, the Democratic Republic of Congo, Mozambique and Madagascar.1
The Indian subcontinent still carries the highest burden of leprosy and more than half of all cases diagnosed in the UK have been in patients who originate in the Indian subcontinent.2,3
Leprosy is classified into subtypes according to the Ridley-Jopling system, which relies on the clinical and histological features, and the bacterial index (a measure of the bacterial load) if available.4
The subtype of leprosy that patients develop is determined by their cell-mediated immune response to infection. Classifying leprosy is important because it determines how infectious patients are, what drug regimen they should use and their risk of complications and prognosis.
In the polar forms of the disease, patients have either strong or poor cell-mediated immunity, resulting in paucibacillary or tuberculoid leprosy (TL) and multibacillary or lepromatous leprosy (LL) respectively.
Patients with TL are not very infectious because they have few skin lesions with no detectable mycobacteria. However, patients with LL are infectious due to the presence of multiple lesions with high bacterial loads.
Borderline forms of leprosy are significant because they are immunologically unstable and are at risk of undergoing leprosy 'reactions' which are immunological phenomena.5 Typically, TL presents with a single or a few well-defined hypopigmented or erythematous macules. However, LL is clinically very different, presenting either as multiple nodules or widespread skin infiltration. Borderline leprosy cases have more numerous, larger and less well-defined lesions compared with TL.
Incubation periods can be very long; two to five years for paucibacillary leprosy and eight to 12 years for multibacillary leprosy. Therefore, disease must be suspected in individuals long after their return or immigration to the UK.
Section 2: Making the diagnosis
Skin lesions are common and usually occur before signs of nerve impairment. Patients may develop macules, papules or nodules. These may be hypopigmented, flesh-coloured or erythematous. Skin may also be thickened from infiltration, which can cause secondary alopecia in hair-bearing areas.
Nasal mucosa can be infected, with patients complaining of nasal stuffiness and epistaxis. If undetected, this can progress, leading to saddle deformity due to septal perforation and destruction of the anterior nasal spine.
Peripheral sensory, motor and autonomic nerves may be involved, producing loss of sensation, muscle weakness and reduced sweating, with characteristic dryness of the skin. Affected nerves may be enlarged and palpable, and sometimes tender. The posterior tibial nerve is most commonly affected, causing anaesthesia of the soles of the feet. Other nerves that are often affected include the ulnar, median, radial, lateral popliteal, facial and greater auricular nerves.
Loss of motor function produces disability and impaired sensation leads to inadvertent trauma, causing ulceration and secondary infection (including osteomyelitis). Eye involvement in leprosy can predispose to blindness, due to a combination of factors - lagophthalmos (from facial nerve damage), corneal ulceration (from trigeminal nerve damage), iridocyclitis and secondary cataract formation.
Borderline leprosy lesions
Some diseases, including skin diseases, may share clinical similarities and be mistaken for leprosy (see box below).
These should be considered in suspected cases of leprosy. Many of these skin conditions are usually not diagnostically difficult on referral to a dermatologist. Most UK dermatologists will have little or no experience of leprosy, but they will be able to exclude these other diseases and should certainly consider leprosy in atypical presentations.
Vitiligo is a common dermatological disease, so it is worth noting that vitiliginous lesions are by definition depigmented, rather than hypopigmented. Vitiligo does not usually pose diagnostic uncertainty for dermatologists. Where there are diagnostic dilemmas, a skin biopsy will help because most of the skin diseases considered in the differential diagnosis, as well as leprosy itself, have distinct histopathological features.
A late diagnosis risks the patient developing progressive disability and transmitting infection. Delays in diagnosis are common in non-endemic countries and are associated with referrals to a variety of specialists.
For example, nerve pain can be confused with joint pain and some patients have been incorrectly diagnosed with arthritis, while cases of neuropathic ulceration have been mistaken for diabetic neuropathy and orthopaedic surgeons have sometimes been referred patients with osteomyelitis, deformities of the hands and feet, or nerve damage presumed to be due to entrapment, when the underlying diagnosis of leprosy has been missed.2
|DIFFERENTIAL DIAGNOSES FOR LEPROSY|
|SKIN DISEASES||SYSTEMIC DISEASES|
Diffuse cutaneous leishmaniasis
Section 3: Managing the condition
Leprosy is clinically diagnosed by the presence of skin lesions, which are often anaesthetic and thickened, and/or tender peripheral nerves.
In endemic regions, the clinical diagnosis is often corroborated on the same day by performing slit skin smears for the detection of acid-fast bacilli (which gives the bacterial index). Skin smears are highly specific but have low sensitivity. They are usually negative in paucibacillary leprosy.
A skin biopsy should also be performed to confirm the clinical diagnosis and categorise the type of leprosy. In the case of pure neuritic leprosy (leprosy without skin lesions), the diagnosis is often made only after excluding other peripheral neuropathies and performing a nerve biopsy to confirm it.
Confirmed cases of leprosy receive the WHO-recommended multidrug therapy regimens, consisting of monthly rifampicin and daily clofazimine and dapsone for a minimum of six to 12 months, depending on whether infection is paucibacillary or multibacillary.
Rifampicin is highly bactericidal and patients are no longer infectious after the first dose.6
Consider referral to neurology for a fuller neurological assessment, to determine even mild nerve impairment and muscle weakness. If these are detected, the patient would benefit from physiotherapy and occupational health input.
Patients with leprosy should also undergo ophthalmology assessment, even in the absence of obvious eye disease. It is especially important that reactions are managed by specialists - patients require treatment with high-dose and long-term steroids, which are associated with significant adverse effects.
Therefore, immunosuppressants are sometimes given in addition as steroid-sparing agents.7
Reactions are serious immunological complications that can occur before, during or many years after the completion of drug therapy. They most commonly occur after starting drug therapy for leprosy. Reactions can also be the presenting feature of new cases of leprosy because preceding skin lesions and any mild nerve impairment may have gone unnoticed by the patient.
Type 1 reactions are the most common form, occurring in 30% of those with borderline leprosy. They are characterised by acute inflammation of existing skin and/or nerve lesions, or the development of new inflamed skin and/or nerve lesions. There may be oedema of the face, hands and feet, but systemic symptoms are unusual.
Type 2 reactions are less common than type 1, and occur mainly in patients with LL. Type 2 reactions are also known as erythema nodosum leprosum because patients present with multiple, tender, erythematous papules and nodules. Systemic symptoms are common and patients report fever, uveitis, neuritis and arthritis.
Reactions are a major cause of nerve function impairment and should be regarded as a medical emergency because any delay in treatment is associated with a significant risk of permanent nerve damage.
Section 4: Prognosis and follow up
Leprosy is still endemic in many regions of the world and although patients who complete a course of antibiotic treatment may no longer be infectious, they can face long-term complications.
Leprosy patients require long-term follow-up and regular neurological assessment for any deterioration in sensory or motor function, which is indicative of a silent neuropathy.
Household contacts of index cases are particularly at risk of infection and should be screened at the time of diagnosis of the index case.
Delays in diagnosis and management will increase the risk of developing nerve damage and permanent disability.
Section 5: Conclusion
Diagnosing leprosy is difficult, given its many clinical presentations and because it often manifests years after patients have left endemic regions, owing to its long incubation period.
Furthermore, patients with a history of leprosy (who are still at risk of complications) may fail to disclose their diagnosis to their GP, because leprosy is still stigmatised in many parts of the world.
Suspected cases should be promptly referred to secondary care dermatology or neurology services for investigation because delays in diagnosis and management will increase the significant risk of developing nerve damage and permanent disability.
In particular, leprosy should be considered in cases of unexplained neuropathy. In confirmed cases, GPs can play an important role in identifying and screening close contacts at risk of infection.
- Contributed by Dr Mahreen Ameen, Royal Free London NHS Trust and former visiting lecturer at Addis Ababa University and ALERT hospital, Ethiopia
1. WHO. Global leprosy situation, 2010. Weekly Epidemiological Record 2010; 85: 335-48.
2. Lockwood DN, Reid AJ. The diagnosis of leprosy is delayed in the United Kingdom. Q J Med 2001; 94: 207-12.
3. Gill AL, Bell DR, Gill GV et al. Leprosy in Britain: 50 years experience in Liverpool. Q J Med 2005; 98(7): 505-11.
4. Ridley DS, Jopling WH. Classification of leprosy according to immunity. Int J Lepr 1966; 34: 255-73.
5. Rodrigues LC, Lockwood DN. Leprosy now: epidemiology, progress, challenges, and research gaps. Lancet Infect Dis 2011; 11: 464-70.
6. Shepard CC, Levy L, Fasal P. Rapid bactericidal effect of rifampin on Mycobacterium leprae. Am J Trop Med Hyg 1972; 21: 446-9. 7. Brandsma JW. Prevention of disability in leprosy: the different levels. Indian J Lepr 2011: 83(1): 1-8.
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