REVIEW Leprosy Is a Communicable Disease Due to Chronic Infection Caused by Mycobacterium Lep- Rae, Principally Affecting the Skin and Peripheral Nerves

Home , Borderline leprosy, Lepromatous leprosy, Lesion, Tuberculoid leprosy

194 PRACTICAL NEUROLOGY

INTRODUCTION REVIEW Leprosy is a communicable disease due to chronic infection caused by Mycobacterium leprae, principally affecting the skin and peripheral nerves. It does not affect the spinal cord or brain Pract Neurol: first published as on 1 August 2004. Downloaded from in man. It is still one of the major health problems of developing countries. Case diagnosis and detection are not always clear or consistent, and reporting in many parts of the world is incomplete or irregular. Indeed, because of the fear, shame and social stigma associated with the disease, leprosy is generally under-reported. However, simplifi ed WHO diagnostic criteria along with community awareness programmes have helped in reducing social stigma and improving case detection. The WHO estimated there were 10–12 million cases in the 1980s. The latest estimate (1994) is 2.4 million cases, a reduction of over three-quarters, mainly due to the widespread use of multidrug therapy in leprosy control (WHO 1994). According to the WHO, 543 662 new cases were detected in 2003, and of these 473 658 were from India. Sri Lanka had reported 1925 new cases. Around 80% of all registered leprosy cases in the world are confi ned to fi ve countries: India, Brazil, Mozambique, Nepal and Madagascar http://pn.bmj.com/ in descending order of prevalence. South-east Asia has 75% of all cases, Africa 12%, and the Americas 8%. Major endemic countries in 2003 were Brazil, India, Madagascar, Mozambique

and Nepal. Approximately 2.2 billion people on September 26, 2021 by guest. Protected copyright. live in areas where leprosy is an important prob- lem – where the estimated prevalence is over 1 case per 10 000 – and thus may be considered Leprosy

Saman B. Gunatilake* and Sunil Settinayake† *Department of Medicine, Faculty of Medicine, University of Kelaniya, PO Box 6 Thalagolla Road, Ragama, Sri Lanka; †Director, National Leprosy Control Programme, Room 21, National Hospital, Colombo, Sri Lanka. E-mail: [email protected] Practical Neurology, 2004, 4, 194–203

© 2004 Blackwell Publishing Ltd AUGUST 2004 195 at signifi cant risk of contracting the disease. Al- Norway, in 1873 in fresh mounts of scrapings though leprosy is now prevalent only in tropical from a leproma from a Norwegian patient, and countries, it is unlikely that this is just due to the it was the fi rst reported bacterial pathogen of a climate because it was formerly very common in chronic disease in humans. M. leprae is an acid- temperate regions of the world. fast rod-shaped bacillus. It is an obligate intra- Pract Neurol: first published as on 1 August 2004. Downloaded from cellular bacillus multiplying mainly inside the HISTORICAL BACKGROUND macrophages of the skin and peripheral nerves. Leprosy is not a disease of modern civilization It closely resembles the tubercle bacillus and oc- but one of the oldest scourges of mankind. Most curs in large numbers in the lesions of leproma- probably it originated in ancient India where it tous leprosy (Fig. 1). was referred to as ‘Kushtha’. Veda manuscripts The infected human being is considered to be written as early as 1400 BC included instructions the only source of infection. The infective capac- for the prevention of leprosy. The fi rst authentic ity of multibacillary lepromatous cases is 4–11 description of leprosy and its treatment is given times greater than that of paucibacillary tuber- in ‘Sushruta Samhita’, a treatize written in India culoid cases. Prolonged and/or close contact in 600 BC by Sushruta, an eminent surgeon of is considered to be necessary for transmission. that time. In China leprosy was recorded in the Only the ulcerated or abraded skin lesions of pa- Nei Jing, one of the earliest Chinese medical tients with multibacillary leprosy are infective. classics (400 BC), in which its clinical features Untreated lepromatous patients may discharge were described under the name ‘Da Feng’. as many as 100 million bacilli from their nasal The disease was probably brought to the Med- secretions every day (Waters 1981) iterranean region by the soldiers of Alexander the Great returning from their Indian campaign CLINICAL COURSE AND FEATURES in 327–326 BC. The earliest description of true The natural history is very variable. The incu- leprosy in Europe was recorded by Aretaeus in bation period is usually 2–5 years, but may be about 150 AD in Greece. Hippocrates probably as long as 20 years. Most people who come into did not know true leprosy, because his descrip- contact with even infectious lepromatous pa- http://pn.bmj.com/ tion did not mention any neurological mani- tients do not develop any symptoms or signs festations. The term leprosy is derived from the of leprosy although they may have experienced Greek word lepros, which means scaly. infection, which they have overcome. Leprosy was probably unknown at the time The nature of the lesions and the progress of

of Moses and the word tsara-ath in the Old the disease depend on the immune response to on September 26, 2021 by guest. Protected copyright. Testament did not mean leprosy but a group of M. leprae. The majority of those who develop diseases with obscure identities, although when clinical effects mount a strong cell mediated the Old Testament was translated into Greek in immune response and develop tuberculoid about 200 BC tsara-ath became lepra. The disease certainly existed at the time of Christ as is clear from references in the New Testament. Leprosy was common in Europe and Great Britain in the 14th century and there were about 19 000 leprosaria in Europe. In the Middle Ages the leprosy sufferer was considered as unclean not only by society but also by the church, and was expected to live outside the city walls. A con- tinuing effort is still being made to minimize the stigma associated with leprosy. The Fifth Inter- national Leprosy Congress in 1948 adopted a resolution to abandon the word leper for leprosy patient. Hansen’s disease is preferred by some for the same reason.

AETIOLOGY M. leprae is a species in the order Actinomyc- etales and the family Mycobateriaceae. This bacillus was ﬁ rst seen by Hansen in Bergen, Figure 1 Mycobacterium leprae bacilli (dark blue rods) in nasal mucus.

leprosy. The minority that mount a weak cell tous. Sensation over the affected area is normal mediated immune response, or none at all, de- or slightly impaired, while sweating and hair velop lepromatous leprosy. Between these two growth are usually unaffected. The peripheral extremes there is a borderline form, which may nerves are normal. Slit skin smears (see below) show some characteristics of tuberculoid and taken from the lesions are either negative or con- Pract Neurol: first published as on 1 August 2004. Downloaded from some of lepromatous leprosy. If the bacilli do tain only a few bacilli. obtain a foothold the defence mechanisms of the host may create an early reaction, which is Tuberculoid leprosy called ‘indeterminate’, because the skin lesion In tuberculoid leprosy, patients have a single le- is too immature to be classifi able. (Ridley & sion or a few randomly placed hypopigmented Jopling 1966). or erythematous lesions in the skin (Fig. 2). Leprosy may also be classifi ed according to These lesions may be macular or infi ltrated, the bacillary load and this is used extensively but the edges are sharply demarcated and the in deciding treatment and prognosis. Multi- border fi nely papulated. Their size ranges from bacillary leprosy contains all lepromatous, bor- less than 1 cm to those that cover entire body re- derline lepromatous and also those borderline gions, such as the cheek, thigh or buttock. Over tuberculoid patients positive for M. leprae in the lesions, sensation is impaired, sweating is di- the skin smears. Paucibacillary leprosy con- minished, and hair is eventually lost as a result tains indeterminate, tuberculoid and also those of damage to the dermal nerves. Well-defi ned borderline tuberculoid patients who are smear edges and sensory loss are characteristic features negative. of tuberculoid leprosy. There may be damage to nerve trunks in the vicinity of the skin lesions, Indeterminate leprosy and on occasion painful mononeuropathies de- The indeterminate lesion is frequently the ear- velop with swollen or enlarged nerves. (Sabin liest manifestation of leprosy and may heal et al. 1993). spontaneously, remain unchanged for months In some patients the presentation can be with or years, or progress towards the tuberculoid neurological symptoms due to infl ammation of http://pn.bmj.com/ or lepromatous forms. A single macule or a few peripheral nerve trunks, albeit with skin lesions poorly defi ned macules occur in the skin. In already present but not brought to medical at- pigmented skin the macule is mildly hypopig- tention (Table 1). In order of frequency the af- mented, but in lighter skin slightly erythema- fected nerves are: ulnar immediately above the

elbow, posterior tibial near the medial malleolus on September 26, 2021 by guest. Protected copyright. of the tibia, and the lateral popliteal (common peroneal) nerve where it winds round the neck of the ﬁ bula. The median, facial, trigeminal, greater auricular and supraorbital are other nerves that are frequently affected. The enlarged cutaneous nerves can sometimes be palpated or seen adjacent to skin lesions. Greater auricular nerve enlargement can be easily seen in the neck when the head is turned to the opposite side (Fig. 3) and this may be associated with skin lesions in the cheek.

Figure 2 Tuberculoid leprosy: hypopigmented anaesthetic macule.

Table 1 Common neurological presentations of leprosy

Ulnar claw hand with sensory loss over the ulnar distribution and a thickened ulnar nerve at the elbow (Fig. 4) Wrist drop and thickened radial nerve Pract Neurol: first published as on 1 August 2004. Downloaded from Foot drop with sensory loss over the medial side of the foot and thickened common peroneal nerve felt over the neck of the ﬁ bula (Fig. 5) Unilateral progressive facial palsy http://pn.bmj.com/

Figure 3 Enlarged greater auricular nerve. on September 26, 2021 by guest. Protected copyright.

Lepromatous leprosy In lepromatous leprosy, a progressive symmet- The leprosy bacillus multiplies freely in lepro- ric polyneuropathy favouring cool regions is the matous patients, and the disease disseminates chief manifestation (Sabin et al. 1993). There is widely. Early lepromatous leprosy presents as also damage to peripheral nerve trunks, result- hypopigmented or slightly erythematous mac- ing in superimposed mononeuropathies that ules with little or no sensory changes. These may evolve into a mononeuritis multiplex. De- macules are small but may grow and coalesce formities such as claw hand, foot drop and loss to cover large areas of skin. At this stage clini- of terminal phalanges are common in these pa- cal diagnosis is diffi cult, but skin smears usu- tients and non-healing trophic ulcers are seen ally demonstrate acid-fast bacilli and biopsy frequently (Fig. 6). specimens are diagnostic. If not treated in the The eyebrows begin to thin at the lateral macular stage, infi ltrations of the skin gradu- margins and may disappear completely. Due to ally increase, and nodules may develop. The infection the testes become atrophic leading to heaviest infi ltrations are in the cooler areas gynaecomastia and sterility. The nasal mucosa of the body such as the earlobes, face, exterior is thickened causing a stuffy nose, and if the lar- surfaces of the extremities, and buttocks. Facial ynx is involved the voice may change. Rapidly infi ltration results in the thickening of the ear multiplying leprosy bacilli overwhelm the host, lobes, nose and cheeks giving the appearance of and are found in the lacrimal secretions, nasal leonine facies. mucosa and discharge, discharge from ulcerated At this stage, cutaneous nerves are frequently skin nodules, sputum, breast milk, blood, semen enlarged, with sensory loss in the hands and feet. and faeces.

Visual impairment and blindness occur fre- before motor changes. This form of leprosy gives quently, particularly in patients with advanced rise to diagnostic diffi culties because the skin le- lepromatous leprosy, as a result of: sions are absent, but the isolated nerve lesion(s) • Corneal ulceration and scarring are due to and the enlarged, thickened nerve(s) are reliable exposure keratitis as a result of lagophthal- clues to the diagnosis. The diagnosis may be con- Pract Neurol: first published as on 1 August 2004. Downloaded from mos if the facial nerve is damaged, reduced or fi rmed by a carefully taken biopsy of a cutaneous absent corneal sensation if terminal branches branch of a clinically affected nerve (see below). of the trigeminal nerve are damaged, and also from direct infection by M. leprae. In some Leprosy and AIDS advanced cases corneal lepromas may be seen In contrast to infections with M. tuberculosis, M. at the lateral part of the cornea-scleral junc- avium-intracellulare and M. kansassi, there is lit- tion. tle or no interaction between leprosy and HIV. • Iris involvement may be either in the acute Lowering of T-cell mediated immunity in AIDS form of iridocyclitis, as part of the erythema would be expected to cause a deterioration of nodosum leprosum reaction (see below), or the disease in individuals suffering from lep- as a chronic process. rosy, a shift toward more multibacillary disease, • Cataract may be caused by or made worse by and an increase in the incidence of new cases. iridocyclitis, or the use of systemic steroids in However, leprosy does not appear to be more reactions (see below), and by intraocular in- frequent in HIV positive than HIV negative vasion with bacilli. individuals in areas where both infections are Because the eye lesions usually develop insid- endemic (Lucas 1993). This paradox requires iously, often without pain or other symptoms, it further study of large populations in endemic is essential that the eyes of every leprosy patient areas of both diseases. are examined both in the fi eld and in hospital. Leprosy in pregnancy Borderline leprosy Leprosy has no direct effects on a pregnant Borderline leprosy, sometimes called dimor- mother. It has no effect on the growth of the http://pn.bmj.com/ phous or intermediate leprosy, is the most com- fetus, leprosy treatment can be continued, and monly encountered type and has features of the drugs are not known to have any teratogenic both the tuberculoid and lepromatous forms. effects. So if a leprosy patient becomes pregnant This is an unstable form of the disease that may the patient should be reassured and provided

evolve to tuberculoid leprosy, or if untreated with normal antenatal care. The leprosy treat- on September 26, 2021 by guest. Protected copyright. downgrade to lepromatous leprosy. Borderline ment should be continued as in any other case. leprosy skin lesions may be erythematous or copper-coloured infi ltrated patches, raised in DIAGNOSIS the centre and sloping towards the periphery, Experienced clinicians accurately diagnose presenting an inverted saucer appearance. Hy- most cases with advanced lesions, purely on the poaesthesia and impairment of hair growth are physical fi ndings: defi nite loss of sensation in characteristic of these borderline skin lesions. one or more skin lesions. But leprosy can be mis- Borderline patients are particularly prone to taken for several diseases (Tables 2 and 3). The damage to nerves, often early in the disease, and diagnosis should be considered in any atypical frequently end up with crippling deformities or unfamiliar skin disorder, and in any obscure such as claw hand, foot drop and trophic ulcera- peripheral nerve disorder, in a patient from an tions. Affected nerve trunks are swollen, pain- endemic area such as Asia, Africa, the Pacifi c is- ful and tender. Facial nerve paralysis frequently lands, or South America. It is worth noting that leads to exposure keratitis (see above). the deep tendon refl exes are preserved until the late stages, despite pronounced sensory loss, be- Primary neuritic leprosy cause the neural involvement is mostly of the This is a form of tuberculoid and borderline distal intracutaneous nerves. The most recent leprosy with no evidence or history of skin le- WHO recommendations for diagnosis in fi eld sions and where the nerves are invaded by the M. programmes are based on the number of skin leprae bacillus. It is characterized by neurologi- lesions: between 1 and 5 is classifi ed as pauci- cal manifestations caused by the asymmetrical bacillary leprosy, more than 5 is classifi ed as involvement of usually one or, at times, several multibacillary leprosy. If in doubt the patient is peripheral nerve trunks. Sensory changes occur treated as for multibacillary leprosy.

Figure 4 Tuberculoid leprosy: ulnar claw hand with a hypopigmented skin lesion. http://pn.bmj.com/ on September 26, 2021 by guest. Protected copyright.

Figure 5 Tuberculoid leprosy: foot drop with a large skin lesion.

Figure 6 Lepromatous leprosy: a trophic ulcer and bilateral claw hands.

Table 2 Skin lesions that may be mistaken for leprosy BACTERIOLOGICAL EXAMINATION

MACULAR SKIN LESIONS RAISED SKIN LESIONS NODULAR SKIN LESIONS Skin smear Vitiligo and leucoderma Tuberculous skin lesions Post kala azar This is necessary only to establish proof of the Tinea versicolor Lupus vulgaris Cutaneous or dermal disease and to assist in correct classifi cation. It is Pract Neurol: first published as on 1 August 2004. Downloaded from Pityriasis versicolor Lupus erythematosus Leishmaniasis not necessary if there is sensory loss. Slit-scrape Granuloma annulare Syphilis biopsy of the skin lesions is recommended. The Tinea or ringworm Onchocerciasis most active part of the lesion should be chosen Sarcoidosis Mycosis fungoides and this will be at the edge in tuberculoid lep- Psoriasis Sarcoidosis rosy and in the centre in the lepromatous type. It is essential that the incision reaches the sub- cutaneous fat, otherwise the deeper layers of the Table 3 Differential diagnosis of the neurological features of leprosy dermis may not be included in the biopsy. The skin lesion is cleaned with ether and a fold is Peripheral neuropathy (diabetes, hereditary sensory neuropathy, etc.) fi rmly held between the thumb and forefi nger Amyloidosis with peripheral neuropathy and thickened nerves of the left hand to render it avascular. With a Cervical outlet syndrome scalpel an incision is made about 5 mm long Syringomyelia and 3 mm deep. The blade is then turned at Distal spinal muscular atrophy right angles to the cut and the wound is scraped Motor neurone disease several times so tissue fl uid and pulp collect on Scleroderma because the deformities can mimic leprosy deformities one side of the blade. This is gently smeared onto a glass slide. Smears are fi xed by heat and stained by the Ziehl–Neelsen method. Acid fast bacilli will always be found in lepromatous leprosy and in borderline leprosy, but usually not in tuberculoid leprosy. However, the quality of skin smears and of microscopy has been the http://pn.bmj.com/ weakest link in most elimination programmes. Fewer than 15% of newly diagnosed cases show positive smears under fi eld conditions. Moreo- ver, in many endemic countries this procedure

carries the risk of transmitting HIV and hepa- on September 26, 2021 by guest. Protected copyright. titis. Therefore, the current WHO recommen- dation is that skin smears are not a prerequisite At present dapsone, rifampicin for diagnosis.

and clofazimine are the Skin biopsy This is essential for correct classifi cation and principal antileprosy drugs for diagnosis when skin smears are negative for bacilli. The most active part of the lesion is biop- and two or more are given sied, again at the edge in tuberculoid leprosy and in the centre in the lepromatous lesions. It is es- concurrently as standard sential that the incision reaches the subcutane- ous fat, otherwise the deeper layers of the dermis treatment may not be included in the biopsy. Skin biopsy is indicated if multibacillary (lepromatous and borderline-lepromatous) leprosy is considered likely, but no M. leprae have been seen in the skin smears, and in cases of paucibacillary (tuberculoid and indeterminate) leprosy if sensory impairment is not certain. Skin biopsy may be useful in children with tuberculoid lesions in whom sensory defi cit cannot be verifi ed with certainity.

Nerve biopsy effects are rare: malaise, haemolytic anaemia, A nerve biopsy is necessary in a purely neu- leucopenia, methaemoglobinaemia, drug fever, ral case. A thickened sensory nerve is chosen, nephropathy, acute peripheral neuropathy, such as the greater auricular in the neck, the ﬁ xed drug eruptions, toxic epidermal necroly- antebrachial cutaneous nerve in the forearm, sis, exfoliative dermatitis and hepatitis. The Pract Neurol: first published as on 1 August 2004. Downloaded from the radial at the lateral aspect of the wrist, the neuropathy due to dapsone is purely motor and femoral cutaneous in the thigh, the sural in the is not associated with nerve swelling, pain and leg or the superﬁ cial peroneal on the dorsum worsening of the skin lesions as seen with reac- of the foot. tions (see below). Dapsone by itself is no longer used. This is The lepromin test due to its slow and limited effectiveness and the The lepromin test is a guide to the cell-medi- development of resistance. Because of the long ated immunity status of the patient. Lepromin duration of treatment required in lepromatous is a suspension of autoclaved M. leprae, ob- leprosy, irregular and inadequate doses of dap- tained from leprosy patients or armadillos – the sone taken by patients can lead to secondary re- infected armadillo’s liver may contain as many sistance within 3–20 years. Secondary resistance as 1000 million bacilli per gram of tissue (Bry- has been detected wherever dapsone has been ceson 1990). 0.1 mL of lepromin is injected in- used as monotherapy, the highest frequency so tradermally into the forearm and the 48–72 h far being 40% in central Burma (Pearson 1981). and 3–4 week readings are recorded. Reactions Primary resistance, though rare, occurs if a pa- measuring greater than 5 mm are positive and tient is infected with a resistant strain picked up indicate strong cell mediated immunity. The from a patient with secondary resistance. lepromin test is not of diagnostic help because it is usually negative in lepromatous leprosy. Rifampicin Rifampicin has proved its value as an addition to TREATMENT leprosy therapy since 1970. It is a strongly bac- Until 1941 there was no really effective antile- tericidal drug and rapidly effective in relieving http://pn.bmj.com/ prosy drug, when Guy Faget introduced a disub- nasal symptoms in lepromatous leprosy and in stituted derivative of dapsone intravenously at healing ulcerated skin nodules. It is given as sin- the National Leprosarium, Carville, USA. gle oral dose of 600 mg once every 4 weeks on an Treatment should be started as soon as a empty stomach (Jopling 1978). Rifampicin pro-

defi nite diagnosis has been made and the case duces a reddish-brown colour in sputum, urine on September 26, 2021 by guest. Protected copyright. classifi ed as multibacillary or paucibacillary. and sweat. Other adverse effects include nausea, Multi-drug therapy is now the standard treat- abdominal discomfort, a fl u-like syndrome and ment. Lepromatous patients need not be kept rarely a toxic hepatitis. The fi rst two cases of ri- isolated as in the past because they do not dis- fampicin resistance were reported in 1976 and charge any viable bacilli after starting treatment subsequently other cases have been reported in with rifampicin. Besides the drug treatment, patients on monotherapy. leprosy patients need moral support and reas- surance so they can regain their self-confi dence Clofazimine and self-respect. Nutritional defi ciencies and Clofazimine appears to have a remarkable action anaemia should be corrected. on erythema nodosum leprosum (see below), At present dapsone, rifampicin and clofaz- and on the course of lepromatous leprosy. In imine are the principal antileprosy drugs and the multi-drug treatment regime clofazimine is two or more are given concurrently as standard given as a daily dose of 50 mg supplemented by treatment. With the judicious use of these drugs a monthly loading dose of 300 mg. The main leprosy can defi nitely be arrested in the individ- adverse reaction is deep and persistent redness ual and controlled in the community. of the skin followed by dark pigmentation.

Dapsone TREATMENT REGIMENS Dapsone is slowly bactericidal and almost Anti-leprosy drugs are no longer given singly completely absorbed after oral administration. but as multi-drug regimens, necessary to over- Clinical improvement is usually seen within come the development of resistance to dapsone 3–6 months. The adult dose is 100 mg as a sin- and other drugs. Two standard regimens are rec- gle daily dose and it is well tolerated. Adverse ommended (WHO 2000).

Multibacillary leprosy (more than 5 skin cal features are similar in both downgrading and lesions) reversal reactions. There may be fever in severe For adults: cases sometimes lasting several months. Ery- • rifampicin 600 mg once a month supervised, thema and swelling of skin lesions occur. The i.e. given when patients attend clinics, or given hands and feet may be swollen and tender. Nerve Pract Neurol: first published as on 1 August 2004. Downloaded from at fi eld visits; involvement is common with swelling and ten- • plus, dapsone 100 mg daily, self-adminis- derness of the nerves. The neuritis causes severe tered; sensory loss, and paralytic deformities such as • plus, clofazimine 50 mg daily, self-adminis- claw hand, foot drop and facial paralysis. The tered, and 300 mg once a month supervised. disease tends to move toward the tuberculoid This triple drug regimen must be given for a form. By this mechanism, patients with the near fi xed period of 12 months. This can be diffi cult lepromatous forms may self-heal and end up to achieve; strategies used include health edu- with classical burned-out leprosy. cation, regular fi eld clinics and home visits by Reversal reactions have to be differentiated healthcare workers, patients accompanied by a from relapse of the underlying disease for the family member to clinics so he or she can super- correct management. Risk of relapse is high in vise drug taking at home, tracing defaulters, etc. patients receiving inadequate treatment. The di- The duration of treatment should be extended agnosis of relapse can be confi rmed by slit-skin in patients who have not responded satisfacto- smear examination or skin biopsy. A therapeutic rily within 12 months. trial with steroids may also help differentiate between a relapse and reversal. In reversal reactions Paucibacillary leprosy (1–5 skin lesions) improvement is seen within four weeks, while in For adults relapse the lesions subside but reappear. • rifampicin 600 mg, supervised once a month for 6 doses; Erythema nodosum leprosum (type 2 • plus, dapsone 100 mg daily, self-administered lepra reactions) for 6 months. This is a type III humoural hypersensitivity re- http://pn.bmj.com/ action seen only in lepromatous and borderline LEPRA REACTIONS cases. It usually occurs when patients have been The course of leprosy, whether treated or not, is under treatment and the bacilli are disintegrat- often interrupted by acute reactional episodes. ing and releasing antigenic material. This reac-

These may be ushered in by immunological tion may be intermittent or continuous. Clinical on September 26, 2021 by guest. Protected copyright. changes following effective drug therapy, and features include fever, transient crops of small reduction of the bacillary load. Reactions may painful red nodules lasting a few days, painful also occur spontaneously, or may be precipi- red plaques with ulceration, enlarged lymph tated by intercurrent infections, pregnancy and nodes, hepatosplenomegaly, iridocyclitis, orchi- physical stress. Up to 30% of leprosy patients tis, swollen painful joints and painful enlarge- under treatment develop reactions and about ment of nerves. Glomerulonephritis sometimes 80% occur in the ﬁ rst 6 months of treatment. complicates the course, and secondary amy- The two main types are the downgrading and loidosis is a late sequela in some with repeated reversal type reactions (type 1 lepra reaction) in and prolonged episodes. borderline leprosy, and the erythema nodosum leprosum reaction (type 2 lepra reaction) in lep- Treatment romatous leprosy (Ridley 1969). Corticosteroid therapy is used to control the serious aspects of lepra reactions, e.g. neuritis, Type 1 lepra reactions iritis and orchitis. The neuritis is more severe Downgrading is uncommon and is associated and acute in type 1 reactions. Prednisolone with a shift towards lepromatous leprosy in should be started at 40–60 mg daily, and the untreated patients, and in patients who are not dose reduced every 2–4 weeks by 5–10 mg de- receiving adequate treatment. Reversal reac- pending on the clinical response. In type 2 lepra tions are seen in borderline patients when the reactions, nerve damage does not threaten so bacterial load is diminished by treatment, usu- quickly as in a type 1 reaction, and thalidomide ally during the ﬁ rst six months, and represent a is the drug of choice: 100 mg four times a day, delayed type hypersensitivity reaction with an gradually reducing by 100 mg every week. If upgrading of cell mediated immunity. The clini- thalidomide is unavailable or contraindicated,

© 2004 Blackwell Publishing Ltd AUGUST 2004 203 prednisolone should be started. In continuous – including Sri Lanka – have reached the elimi- erythema nodosum leprosum reactions, the nation target (defi ned as reduction of the lep- patients may need treatment with prednisolone rosy prevalence to below one case per 10 000 for long periods (clofazimine can be added in population). doses of 300 mg daily for one to three months Pract Neurol: first published as on 1 August 2004. Downloaded from and then reduced gradually to help with taper- ing off the steroids and to use a lower dose). CONCLUSIONS Resistant cases to the above regime, and steroid dependent cases, should be treated with thalido- • Leprosy is still one of the major health problems of developing coun- mide in addition. tries. • Around 80% of all leprosy cases are confi ned to fi ve countries: India, CONTROL Brazil, Mozambique, Nepal and Madagascar. The principles of leprosy control programmes • Mycobacterium leprae is the causative organism and is a rod shaped are: acid-fast bacillus. • Continuous case detection by population • Clinical features refl ect the cell-mediated immune status of the patient surveys and examination of patient contacts. • Leprosy should be considered in any atypical or unfamiliar skin disorder With a low prevalence in most countries this in a patient from an endemic area. is not cost effective, so the current strategy of • Leprosy should be considered in any motor or sensory peripheral nerve WHO leprosy elimination programmes is to lesion in a patient from an endemic area. raise the community awareness of early signs • Hypopigmented anaesthetic skin lesions are characteristic of tubercu- of leprosy and to dispell the misconceptions loid leprosy. about the disease so that people will visit the • Leprosy is a common cause of neurological deformities such as trophic health clinics. ulcers, claw hand and toes, wrist drop and foot drop. However, the de- • Treatment of all patients with multidrug formity rate has come down drastically as cases are detected and treated therapy. earlier. • Health education of the public and patients. • Multi-drug therapy using dapsone, rifampicin and clofazimine is effec- By educating the general public, much can tive. http://pn.bmj.com/ be done to lessen the social stigma attached to • Community participation is vital for the success of any control pro- leprosy. Community participation is vital for gramme. the success of any control programme. Preven- tion of deformity should be an important com-

ponent of the programme because the stigma on September 26, 2021 by guest. Protected copyright. and fear associated with leprosy stem from the deformities appearing in neglected or improp- ACKNOWLEDGEMENTS erly treated cases. In most leprosy endemic This paper was reviewed by Dr Jeremy Farrar, countries, leprosy control has been integrated Vietnam into the general health services. This increases the accessibility to diagnostic and treatment fa- REFERENCES cilities, and decreases the stigma attached to the Bryceson A & Pfaltzgraff RE (1990) Leprosy, 3rd edn. disease. Chuchill Livingstone, Edinburgh. Jopling WH (1978) Handbook of Leprosy, 2nd edn. Hein- Anti-leprosy vaccines are now under devel- eman, London. opment, and some are being tested under fi eld Lucas S (1993) Leprosy Review, 64, 97–103. conditions, mostly in India, but no conclusive Pearson JMH (1981) International Journal of Leprosy, 49, decisions have been made on a vaccination 417–20. policy. Low infectivity and the long incubation Ridley DS & Jopling WH (1966) International Journal of Leprosy, 34, 255. period of the disease require long follow-up pe- Ridley DS (1969) Leprosy Review, 40, 77. riods and this has made carrying out trials very Sabin TD, Swift TR, Jacobson RR (1993) Leprosy. In: diffi cult in developing countries. The effi cacy Dyck PJ, Thomas PK, Griffi n JW et al., eds. Peripheral of the drug treatment regimens in preventing Neuropathy, 3rd edn, Vol. 2. W.B.Saunders, Philadel- spread of infection has made the search for an phia: 1354–79. effective vaccine less important. Mass scale vac- Waters MFR (1981) Leprosy. British Medical Journal, 283, 1321. cination in endemic areas for an infection with World Health Organization. (1982) WHO. Technical Re- low infectivity would be very problematic. port Series, 675. From among the 122 countries where the World Health Organization (1994) Weekly Epidemio- disease was considered endemic in 1985, 110 logical Report, 20–1.