Leprosy

• Leprosy (Hansen disease) is a chronic infection caused mainly by Mycobacterium leprae, an obligate intracellular, acid-fast bacillus that grows very slowly and favours cooler body sites such as skin, peripheral nerves and the upper respiratory mucosa.
• The type of disease depends on the patient's own cell-mediated immunity: strong immunity gives tuberculoid (TT) disease with a few well-defined, numb patches; weak immunity gives lepromatous (LL) disease with many infiltrated, often symmetric lesions and high bacterial loads.
• Between these poles lie borderline forms (BT, BB, BL); the simplified WHO classification counts skin lesions and nerve involvement and calls cases paucibacillary (PB, 1-5 lesions) or multibacillary (MB, more than 5 lesions or nerve involvement or bacilli on smear). ^[1][4]
• Diagnosis is clinical, built on three cardinal signs: loss of sensation in a skin patch, a thickened peripheral nerve, or bacilli on a slit-skin smear; biopsy with acid-fast staining and PCR support the diagnosis.
• Multidrug therapy (MDT) of dapsone, rifampicin and clofazimine cures the infection: 6 months for PB and 12 months for MB cases, as recommended by WHO; once treatment starts the patient is no longer infectious. ^[4]
• Two inflammatory reactions (type 1, reversal, and type 2, erythema nodosum leprosum) are the main cause of acute nerve damage and must be treated promptly, usually with corticosteroids.

By the end of this page you should be able to:

1. Describe Mycobacterium leprae and explain why its slow growth and intracellular lifestyle shape the disease.
2. Place a patient on the Ridley-Jopling spectrum (TT, BT, BB, BL, LL) and on the WHO PB/MB scheme used for treatment.
3. Recognise leprosy from its skin and nerve findings, apply the three cardinal signs, and choose the investigations that confirm and classify it.
4. Distinguish type 1 and type 2 reactions from relapse or other diseases, and state their main management.
5. Prescribe the standard MDT regimen with drug, dose, route and duration for PB and MB disease in adults and children.
6. Explain prevention (single-dose rifampicin post-exposure prophylaxis, contact screening), disability prevention and low-resource management.

The term "leprosy" is still widely used, but many organisations and affected people now prefer "Hansen disease". Both names appear in current guidance and sources. ^[3]

Globally, leprosy is still a neglected tropical disease reported from more than 120 countries. WHO's 2026 fact sheet records around 200,000 new cases in 2024, most of them in the South-East Asia Region, while CDC's about page cites up to 250,000 people diagnosed each year worldwide; the two sources report slightly different reference years. ^[3][4] In the United States up to 225 cases are identified each year; most affected people became infected in countries where leprosy is more common, and a small number of cases in the southern United States have probably been acquired from infected armadillos. ^[1][3]

Leprosy occurs at all ages, but in endemic countries such as Brazil, Nepal, India and Indonesia cases usually present before age 35. ^[6] The interval from exposure to overt skin and nerve signs is long, so disease is rarely seen in young children. ^[3]

More than 80% of people exposed to M. leprae are thought to resist infection completely. About 17% of household contacts of an infected person test PCR-positive on skin swabs and 4% on nasal swabs, and household contacts make up as many as 28% of new cases and are 4 to 10 times more likely to develop leprosy. ^[6] Men are affected slightly more often than women, with a reported ratio near 1.5:1. ^[6]

The cause is infection with M. leprae (and, in some regions, M. lepromatosis). ^[1][3] No modifiable risk factor for acquiring infection has been established. Risk is increased by prolonged close contact with an untreated person, living in an endemic area, and possibly by zoonotic exposure to armadillos in the southern United States. ^[1][3][6]

Tattooing has been reported as a route of inoculation in a small number of cases. ^[6]

Host immunity is the main determinant of outcome. Most exposed people never develop disease, and the form that appears in those who do depends on their cell-mediated immunity. Monozygotic twins show very high concordance (60 to 85%), which points to a strong genetic influence on susceptibility. ^[6]

M. leprae is an obligate intracellular, acid-fast bacillus. It has never been grown in bacteriological media, but can be grown in the mouse footpad and naturally infects armadillos. ^[1] It multiplies very slowly, dividing about once every 13 days, and favours temperatures of 30 degrees Celsius or less; this explains its tropism for the skin, nerves, ears, elbows, feet and (in men) testes, while the scalp and warmer midline sites are usually spared. ^[1][6]

The bacteria live inside macrophages and Schwann cells and spread along nerves. Because the peripheral nerves are cooler, superficial and well-myelinated, they are the principal target. Chronic infiltration and the immune response lead to demyelination and fibrosis of nerves. Most disability in leprosy is secondary to this peripheral neuropathy, through loss of sensation, weakness and subsequent injury, rather than to direct bacterial damage. ^[6]

The polar ends of the spectrum are set by the host response:

• In tuberculoid disease, strong cell-mediated immunity keeps the bacterial load low, granulomas form, and most bacilli are killed.
• In lepromatous disease, cell-mediated immunity is weak, antibodies are abundant but ineffective, and bacilli multiply unchecked inside macrophages. ^[1][6]

Leprosy is slowly progressive and often presents with numbness before lesions or nerves are clinically obvious. ^[6] The incubation or latency period is 5 to 10 years or more; it is often said that signs may appear up to about 20 years after infection. ^[3][6]

Patients may report:

• Skin patches, nodules or widespread infiltration, often with loss of sensation in the affected area.
• Numbness, tingling or burning in the hands and feet, or weakness of grip or foot drop.
• Nasal stuffiness, nosebleeds or loss of smell.
• Eye problems, including dryness or difficulty closing the eye.
• Fevers, joint pains and painful red nodules during reactions.

Cardinal signs, as given by WHO, are: definite loss of sensation in a pale or reddish skin patch; a thickened or enlarged peripheral nerve with loss of sensation and/or weakness of the muscles it supplies; or bacilli seen on a slit-skin smear. ^[4] Makhakhe lists the same cardinal signs as loss of sensation in a skin lesion, an enlarged peripheral nerve and positive skin smears. ^[6]

Clinical signs by type are summarised in the classification table below. In general:

• Lesions in tuberculoid disease are limited (fewer than 5), well-defined, hypopigmented or erythematous, dry (anhidrotic), hairless and markedly numb; peripheral nerves may be thickened and tender. ^[1][6]
• In lepromatous disease lesions are numerous, symmetric, poorly defined and infiltrated, often in the cooler zones (face, ears, elbows, knees, hands, feet); sensation may be preserved early. Madarosis (loss of eyebrows), thickened skin and nodules are common, and the nasal mucosa, eyes and testes may be involved. ^[1][6]
• Borderline forms show mixed features.

Peripheral neuropathy is the dominant physical finding in many patients and shows up as enlarged ulnar, median, posterior tibial, common peroneal, sural or great auricular nerves, with altered sensation in a glove-and-stocking or nerve-territory pattern, clawing of the fingers, foot drop or neuropathic ulcers. ^[6]

Leprosy is classified in two main ways. ^[1] The Ridley-Jopling five-group system records the immunological position; the simpler WHO system is used to choose treatment.

WHO groups for treatment: ^[4]

• PB case: leprosy with 1 to 5 skin lesions and no bacilli demonstrated on a skin smear.
• MB case: leprosy with more than 5 skin lesions; or any nerve involvement (pure neuritis, or any number of skin lesions with neuritis); or bacilli demonstrated on a slit-skin smear, irrespective of lesion count. ^[4]

Because lesions are numb, hypopigmented patches, leprosy is often mistaken for other hypopigmented dermatoses and for causes of peripheral neuropathy. Consider:

• Vitiligo (depigmented, not numb, sharpest borders).
• Tinea corporis / pityriasis versicolor / pityriasis alba.
• Sarcoidosis, granuloma annulare, cutaneous lupus.
• Diabetic or other peripheral neuropathies without skin lesions.
• Primary neural leprosy, in which only nerve trunks are involved and the skin is normal. ^[1]

The combination of a hypopigmented, anaesthetic patch with a thickened peripheral nerve in an endemic area is highly suggestive.

Slit-skin smears from the earlobes, elbows and knees are used to look for acid-fast bacilli and to calculate the bacterial index. They support diagnosis and are needed for the WHO MB definition. ^[2][4]

Skin biopsy from the edge of an active patch, or nerve biopsy from a thickened nerve, is the definitive diagnostic and classifying test; Ziehl-Neelsen staining with 5% sulphuric acid as the decolorising agent is used, and the presence of acid-fast bacilli confirms the diagnosis. ^[2]

PCR can detect DNA of M. leprae and M. lepromatosis in a skin biopsy. It is useful when clinical and histological findings are unclear, particularly in early or paucibacillary disease, but it complements rather than replaces the standard methods and is available only in specialised laboratories, including the National Hansen's Disease Program in the United States. ^[2]

Nerve conduction studies and electromyography quantify neuropathy. There is no routine blood test specific for leprosy; anti-phenolic glycolipid-1 (PGL-1) antibodies correlate with bacterial load and may mark relapse, but they are not a primary diagnostic tool. ^[6]

There is no formal scoring system. The WHO diagnosis rests on the three cardinal signs listed above. ^[4] WHO global disability grading records eye, hand and foot impairment at diagnosis and during follow-up, which is important for service reporting and prognosis. ^[4]

Management rests on high clinical suspicion, confirmation, examination of household contacts, treatment of the index case for the full duration, and long-term monitoring for reactions and disability. ^[6]

WHO recommends combined therapy with dapsone, rifampicin and clofazimine; the same regimen is given for 6 months in PB and 12 months in MB disease. The edition used here is the WHO Guidelines for the Diagnosis, Treatment and Prevention of Leprosy, 2018, which underpins the current fact-sheet recommendations. ^[4][1][5] MDT kills the pathogen and the patient is no longer infectious once treatment begins; cure follows completion of treatment. ^[4][3] Dosing (from the regimen reproduced in Makhakhe, originally from Belachew and Naafs, 2019) is: ^[6]

In rifampicin-resistant disease, levofloxacin and minocycline can be strongly considered as substitutions, and moxifloxacin, clarithromycin and minocycline are among the major anti-leprosy drugs used in some protocols. ^[6][1] The historic progression from dapsone monotherapy to multidrug regimens began in the 1980s, when the WHO Chemotherapy Study Group recommended combined rather than single-drug treatment; dapsone resistance had appeared in the 1970s. ^[6]

Other practical notes:

• MDT is supplied free of cost by WHO; in endemic-programme settings it is dispensed in blister packs. ^[4]
• Treatment usually lasts 1 to 2 years overall. ^{[3] [1]}
• Patients with suspected dapsone hypersensitivity or G6PD deficiency need particular care; check for haemolysis and follow local guidance.
• In the United States, the National Hansen's Disease Program provides treatment expertise; the HRSA ambulatory clinics are a key resource. ^[1]

Most patients have a reaction at some point, before or after treatment starts. These are not due to the drugs (patients on clofazimine tend to have slightly fewer episodes). ^[1] There are two main types. ^[1][6]

1. Type 1 (reversal) reaction. An enhanced cell-mediated immune response, typical of borderline disease (BT, BB, BL). It appears as oedema and erythema of pre-existing lesions, sometimes with neuritis, new lesions or fever. It represents upgrading towards the tuberculoid pole and is the form most often responsible for acute neuritis and rapid nerve loss.
2. Type 2 reaction (erythema nodosum leprosum, ENL). Seen most often in MB disease. Painful erythematous nodules, often between existing lesions, with moderate to high fever; neuritis, orchitis, lymphadenitis, iridocyclitis, nephritis, periostitis and arthralgia may occur. Lucio phenomenon is a rare, severe necrotising reaction seen in Mexican-ancestry patients with MB disease. ^[1]

Type 1 reactions are treated with corticosteroids (a tapering course of prednisolone is the usual first-line therapy in most programmes), with close neurological monitoring and possible nerve decompression for impending nerve loss. ^[6] ENL is treated with corticosteroids, clofazimine and, where available and appropriate, thalidomide; pain control and prevention of nerve damage guide management. Because exact drugs, doses and durations vary by programme and are set by local and national guidelines, check the local leprosy programme's protocol rather than relying on a single printed dose.

Reactions are an emergency in leprosy because each episode can add permanent disability; treat early and refer if nerve function is threatened.

• Take slit-skin smears and re-examine nerves at intervals to detect relapse.
• Teach patients to inspect hands, feet and eyes daily, to use protective footwear and gloves, and to recognise injuries that occur without pain.
• Eye screening is important in MB disease; a lagophthalmos or early corneal change should be treated.
• Splinting, physiotherapy and reconstructive surgery reduce long-term disability where available.
• Most leprosy specialist programmes offer a full eye, hand and foot screen each visit. ^[1]

Surgery has no role in curing the infection, which is cured by drugs, but reconstructive surgery (tendon transfers, nerve decompression, grafts for nasal collapse) improves function and appearance. Suspected nerve abscess or severe localized nerve pain may require surgical decompression in specialist centres.

• Neuropathy and deformity: claw hand, foot drop, neuropathic ulcers, auto-amputation of digits, nasal collapse, lagophthalmos and corneal ulceration.
• Reactions with acute nerve damage. ^[1][6]
• Ocular involvement: dry eye, iritis, blindness from progressive damage.
• Systemic (MB disease): orchitis with gynaecomastia, nephritis, lymphadenitis, periostitis, arthralgia. ^[1]
• Secondary bacterial infection of insensate feet and ulcers.
• Stigma and social disability, which remain a major burden even after cure. ^[6]
• Lucio phenomenon and severe ENL in some MB patients. ^[1]

Leprosy is curable. With completed MDT the patient is considered cured and no longer infectious; lesions and nerve changes stabilize and often improve, but recovery of lost sensation is limited once fibrosis has set in. ^[4][3] Prognosis is best when diagnosis comes before nerve damage; early treatment is the best prevention of deformity and disability. ^[1] Relapse is uncommon but can occur, usually sensitive to the original MDT; suspected relapse should be confirmed and resistance testing (PCR) used when available. ^[6]

• BCG vaccination affords partial protection and remains the best available prophylaxis in many regions. ^[6]
• Contact screening: examine household, neighbourhood and social contacts of any new case. ^[4][6]
• Single-dose rifampicin post-exposure prophylaxis (SDR-PEP) is recommended by WHO for contacts; one dose reduces risk of disease in contacts. ^[4]
• Active case finding in endemic areas and training of front-line workers improves early detection.
• Disability prevention (self-care, protective footwear, physiotherapy) is the third pillar of long-term control.

Pregnancy. Leprosy can present during pregnancy and the puerperium. MDT is generally continued, as pregnancy may precipitate or worsen reactions; management should be in a specialist programme and referral made early. The available sources here do not give pregnancy-specific dosing modifications; follow local and national guidance.

Children. Paediatric dosing is weight/age-based as above. Leprosy in children is a marker of recent transmission; search for the source case. ^[6]

Immunocompromised and HIV. Leprosy behaves somewhat differently in immunosuppression; IRIS-like reactions have been reported. Treat the infection and seek specialist advice.

Pure neuritic leprosy. Nerve-only disease with no skin lesions is harder to diagnose and may need nerve biopsy; refer early. ^[1]

• A slit-skin smear and a high index of suspicion are the most valuable tools where biopsy is unavailable.
• The WHO cardinal signs, especially a numb hypopigmented patch plus a thickened nerve, are enough to start treatment in many programmes.
• MDT is supplied free of charge; the main barrier is often access to the blister packs and to supervision of dosing. ^[4]
• SDR-PEP is a low-cost, high-value intervention even where laboratory capacity is limited.
• Self-care (daily inspection, appropriate footwear, basic wound care) halves disability and costs almost nothing.
• Refer early for reconstructive surgery, eye care and nerve decompression; where none is available, transfer to a regional centre.

• Leprosy is caused mainly by Mycobacterium leprae (and sometimes M. lepromatosis), a slow-growing intracellular bacillus that favours cooler body sites.
• Type depends on host cell-mediated immunity: tuberculoid (few lesions, high immunity) at one pole, lepromatous (many lesions, low immunity) at the other, with borderline forms between.
• The WHO PB/MB grouping (1-5 vs more than 5 lesions/nerve involvement/smear positivity) decides treatment duration.
• Cardinal signs: numb hypopigmented patch, thickened peripheral nerve, or bacilli on slit-skin smear.
• Diagnosis is clinical; biopsy with acid-fast staining, and PCR when needed, confirm and classify.
• MDT of dapsone, rifampicin and clofazimine cures infection: 6 months PB, 12 months MB, with age/weight-based dosing.
• Once treatment starts the patient is no longer infectious; cure follows completion.
• Reactions (type 1 reversal, type 2 ENL) cause most acute nerve damage; treat promptly with corticosteroids and follow local protocols.
• Disability is mostly secondary to peripheral neuropathy and is preventable with early treatment and self-care.
• Prevention combines BCG, contact screening and single-dose rifampicin prophylaxis.
• Stigma and social disability persist after cure; education and inclusion are part of good care.

Leprosy sits alongside tuberculosis and other mycobacterial infections in the infectious-disease hub; topics such as peripheral neuropathy and skin biopsy technique follow naturally once they are published.