Leprosy☆
Introduction
Leprosy is a chronic granulomatous infection, principally affecting the skin and peripheral nerves, caused by the obligate intracellular organism Mycobacterium leprae.1
There were 407,791 new cases diagnosed and reported to World Health Organization in 2004.2
It continues to be an important health problem worldwide but is most prevalent in India, Brazil, Democratic Republic of Congo, Tanzania, Nepal, Mozambique, Madagascar, Angola, and the Central African Republic.2
The disease causes skin lesions and neuropathy. Secondary complications of the neuropathy can result in deformity and disability. Leprosy remains a stigmatizing disease. Multidrug therapy (MDT), however, which cures the infection, has led to the understanding that leprosy can be effectively treated before disability.3 Since 1985, 14 million individuals have received MDT.2
Transmission of the M leprae is from untreated lepromatous patients. It can persist in the environment; most people have encountered it and mount an immune response against it.
Section snippets
Classification
Classification of the disease is important to determine prognosis and which individuals are infectious. Classification is also important in accurately describing the epidemiology of leprosy, and the type of leprosy will dictate the treatment selected.
There are 2 systems used to classify leprosy patients. The Ridley-Jopling System4 uses clinical and histopathological features and the bacteriological index. The different categories correlate with the activity of the host immune response (Fig. 1).
Clinical features
The clinical features of the disease are determined by the host response to M leprae. Patients commonly present with skin lesions, numbness or weakness caused by peripheral nerve involvement, or more rarely, a painless burn or ulcer in an anesthetic hand or foot. A leprosy reaction may be a presenting feature of the disease.7 Nerve pain misdiagnosed as joint pain may result in a person being labeled as having arthritis.
In nonendemic areas, the diagnosis is frequently delayed because leprosy is
Skin involvement
Early skin lesions may be rather poorly defined hypopigmented or erythematous macules. Sensation in these early stages may be unaltered. The histology of early skin lesions do not show evidence of granuloma formation. There is a nonspecific inflammatory infiltrate around skin appendages.
Tuberculoid disease is characterized by a single or very few lesions. These are macules or plaques with well-defined edges (Fig. 2). The plaques are often flattened in the center. In dark skin, hypopigmentation
Nerve involvement
Nerve involvement in leprosy affects sensory, motor, and autonomic function of peripheral nerves. Sensory loss is the earliest and most frequently affected modality, but a predominantly motor loss can also occur. Granulomatous inflammation of peripheral nerves causes palpable enlargement, which may or may not be painful and causes sensory and motor loss in the distribution of the affected nerve. Enlarged nerves can also be damaged because of entrapment within fibroosseous tunnels. Reactions
Eye involvement
Blindness affects 5.3% of individuals with leprosy. Leprosy is the cause of the blindness in 3.2%.16 Blindness can have devastating consequences for those who probably already have sensory loss of the hands and feet. The disease compromises the eye through nerve damage and by direct bacillary invasion of the skin or eye itself. These factors can occur in combination and result in the 4 main causes of visual loss: lagophthalmos (an inability to close the eyes normally), corneal ulceration, acute
Mucosal involvement
Lepromatous involvement of the nasal mucosa gives rise to the sensation of nasal stuffiness and epistaxis. Infiltration of nasal structures may lead to a saddle deformity due to septal perforation and destruction of the anterior nasal spine.
In advanced lepromatous disease, the tongue may become infiltrated, and deep fissures and ulceration occur. Laryngeal involvement, although extremely rare nowadays, was life-threatening in the days before effective chemotherapy.
Other system involvement and complications
The involvement of other systems is usually seen in lepromatous disease due to bacillary infiltration of structures and organs. Testicular atrophy results from infiltration and the acute orchitis of erythema nodosum leprosum (ENL). Men who have had ENL orchitis should be investigated to define the extent of any hypogonadism where such facilities are available. Amyloid and renal disease rarely complicate leprosy since the advent of MDT.
Type 1 (reversal) reactions
Type 1 reactions occur in borderline disease, and 30% of individuals with borderline leprosy are at risk for type 1 reaction.17 A type 1 reaction is characterized by acute inflammation in skin lesions (Fig. 4) or nerves or both. The skin lesions become acutely inflamed and edematous and may ulcerate. Edema of the hands, feet, and face can also be a feature of a reaction, but systemic symptoms are unusual. Acute neuritis leads to nerve function impairment if not treated rapidly and adequately
Erythema nodosum leprosum reactions
Erythema nodosum leprosum is a reactional state that affects 20% of lepromatous and 10% of borderline lepromatous cases. The greater the infiltration of the skin and the higher the BI, the greater the risk of developing ENL.18 Erythema nodosum leprosum is a systemic disorder affecting many organ systems. The onset is acute, but it may pass into a chronic phase and can be recurrent. Erythema nodosum leprosum is caused by immune complex deposition and is associated with high levels of tumor
Lucio phenomenon
This is a very rare reactional state occurring in lepromatous disease, which presents as painful irregular patches. They become purpuric, and bullae form that break down, leaving widespread areas of ulceration.21 Healing is with scarring. Lucio reaction is associated with severe systemic upset and may be fatal. The mechanism is a cutaneous vasculitis, which is thought to be due to infiltration of the skin, causing an inflammatory microthromboembolic occlusion of the dermal vasculature.22 Lucio
Pregnancy
A systematic literature review of the interaction between leprosy and pregnancy highlighted an association between the development of type 1 reactions and neuritis and parturition when cell-mediated immunity returns to the prepregnant level.23
Erythema nodosum leprosum reactions occur throughout pregnancy and lactation, and the onset of nerve damage is earlier than in those who are not pregnant. There is little evidence that pregnancy promotes infection or relapse of the disease.
Leprosy and HIV
The fear that HIV infection would increase susceptibility to M leprae does not appear to have been realized, nor does it alter the clinical features of leprosy. Leprosy in HIV-positive individuals does not appear to be shifted to the lepromatous pole, nor does it develop quicker. The response to MDT is also unaffected. Reactions in individuals with coinfection may occur with increased frequency, but there are conflicting data concerning the response to treatment in this group.
Latent leprosy
Diagnosis
The diagnosis of leprosy remains a clinical one. The presence of skin lesions with definite sensory loss or thickened peripheral nerves or the demonstration of M leprae on slit-skin smears or on histology of tissue (skin or nerve) is diagnostic (Table 2).
Differential diagnosis
The manifestations of leprosy are protean, and the differential diagnosis is therefore wide. The consideration of leprosy as a diagnosis and adherence to the clinical criteria for diagnosing leprosy will facilitate a correct diagnosis. It can be difficult to diagnose leprosy especially in nonendemic regions or where the prevalence is very low.
Congenital lesions such as nevus depigmentosus have normal sensation and are present at birth. Vitiligo is depigmented rather than hypopigmented.
Investigations
The diagnosis is usually made clinically but is supported by slit-skin smears and skin biopsy.7 Mycobacterium leprae cannot be cultured in vitro.
The BI is a logarithmic scale (1-6) quantifying the density of M leprae on a slit-skin smear and is used to assess response to treatment.
Rarely, nerve biopsy may be needed to confirm the diagnosis and should be performed on a purely sensory nerve (eg, radial cutaneous or sural nerve).
Treatment—chemotherapy
All patients should receive a multidrug combination, and the first-line agents are rifampicin, clofazimine, and dapsone. Multidrug therapy was introduced in 1982 after the emergence of resistance to dapsone-only regimens.27 Since then, there has been debate over how long multibacillary MDT should be taken.
The World Health Organization reduced the recommended treatment period for multibacillary disease from 24 to 12 months (Table 3),6 but this remains under review, and so many authors advocate
Treatment and management of reactions
Leprosy reactions should be managed by a specialist. Reactions may be a presenting feature of the disease or occur during MDT or even after it has been completed. The treatment of type 1 reactions is aimed at controlling the acute inflammation, easing pain and reversing eye and nerve damage. Multidrug therapy should be continued during a reaction. Moderately inflamed skin plaques or neuritis are treated with oral corticosteroids. Different regimens have been used, but prednisolone 40 to 60 mg
Education
It is important to carefully explain the nature of the disease to the patient and that it is curable. It should be emphasized that deformity and disability are not inevitable and that the disease is not hereditary. Multidrug therapy renders those who are infectious safe to close contacts within 72 hours, and a completely normal social life should be encouraged. It should be made clear that transmission of the disease does not occur through sexual contact. Most people diagnosed with leprosy do
Prevention of disability
Minimizing nerve damage by detecting deterioration in nerve function early and instituting steroid therapy quickly is essential in preventing disability.
The prevention of secondary damage to neuropathic areas is essential. It is important to make the patient aware of activities that put these areas at risk and to give advice about orthotics and protective footwear. Individuals should also be advised to undertake self-examination to identify any areas of trauma. It has been demonstrated that
Socioeconomic rehabilitation
General community-based projects involving family and the wider community have been shown to help best with rehabilitation.41 The development of these has been assisted by the International Association for Integration, Dignity and Economic Advancement.
Eradication of leprosy
The eradication of leprosy has not been achieved despite more than 20 years of MDT. Lepromatous patients are highly infectious, and the organism can remain viable outside a human host for many months. The mean incubation time of lepromatous disease is 10 years. These factors make it difficult to completely eradicate the disease.
It must be remembered that dealing with leprosy is not simply a matter of treating the infection of M leprae with MDT. It also requires the prompt management of
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Leprosy morbidity and mortality in Brazil: 2008–2018
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2024, Research SquareDifferent profiles of chemokines, cytokines and cell growth factors in plasma samples from patients with leprosy, leprosy reactions and households contacts
2024, Memorias do Instituto Oswaldo CruzInduction of IL-32 in the immune response of keratinocytes to Mycobacterium marinum infection
2023, Experimental Dermatology
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Dr Walker is supported by grants from LEPRA, the American Leprosy Mission, the Special Trustees of the Hospital for Tropical Diseases, London and the Geoffrey Dowling Fellowship of the British Association of Dermatologists.