LEPROSY (HANSEN'S DISEASE)  An ancient stigmatizing disease of mainly the skin, peripheral nerves, eyes and nose. A notorious cause of blindness, nasal, hand and feet deformities with neurotrophic ulceration and neurotrophic ankle and feet joint changes. Widespread in the world especially in Tropical Africa, South and Central America, India and other parts of Asia. In recent years has declined worldwide with intensified treatment and improved living conditions. In 1986, 5.4 million patients were registered worldwide and this fell to 3.1 million by Feb 1992. Caused by Mycobacterium leprae which is transmitted mainly by household or close contact from the skin and nose. The intracellular organism is recognized in split skin smears from the skin or skin lesions and despite being known since 1873 has not yet been grown in artificial culture. This is a barrier to research which has been overcome to some extent by transmission of the organism to mice, monkeys and armadillos. The incubation period is usually 3 to 5 years or even longer. M leprae is slow growing and divides about once every 12 days. Even after full treatment dormant "persisters" or persisting drug sensitive organisms may still be found in some patients (as in tuberculosis) and relapse is possible.     1. TYPES OF LEPROSY A complex subject and authorities do not fully agree how to classify leprosy. As far as treatment is concerned patients are either paucibacillary (smear negative) usually indeterminate, tuberculoid or tuberculoid/borderline type or multibacillary (smear positive), usually borderline/lepromatous or lepromatous type but detailed classification indicates prognosis. The various types of leprosy can be regarded as a spectrum determined by the cell mediated immunity of the individual such immunity is complex, involves T Lymphocytes in various subgroups and may change over time and along with treatment. Thus the confusing changes in the appearance of lesions in a patient over time and the coexistence of say Borderline and Lepromatous lesions in one patient and the differences sometimes seen when a patient relapses. In addition lepromatous patients have antibodies whose function is unclear except in Erythema Nodosum Leprosum (Type II reaction) 1.1 Indeterminate Leprosy   An early stage of the disease before the type of leprosy has been "determined". May be self healing. Appear as vague hypopigmented macular skin lesions without definite anaesthesia or enlarged peripheral nerves. Skin smear negative. If a definite diagnosis cannot be made best to observe the patient until leprosy can be confirmed or excluded. If definite nerve involvement is shown in skin biopsy histology leprosy can be diagnosed. Otherwise the histology may be non-specific. 1.2 Tuberculoid Leprosy (T type)  In the past some 50% of cases were Tuberculoid or Tuberculoid/Borderline type. Skin smear for M leprae negative and non-infectious. One or two "ring" skin lesions, may be macular or with raised margins are well defined. Lesions hypopigmented and may be erythematous and have anaesthesia. Pain sensation, touch, hot and cold sensation are the modalities lost. Lesions may lack sweating due to sympathetic nerve damage. Non-itching lesions on face, limbs or trunk but almost never found in the axilla, groin or under the hair. The organism appears to favour the cooler parts of the body (cold theory) but may appear on a bald scalp area. Beware of facial lesions which often are non-anaesthetic. M leprae is believed to target Schwann Cells in peripheral nerves and provoke the formation of a granuloma and nerve damage. The nerve damage may involve sensory, motor or sympathetic nerves. The nerves involved may be in the skin lesion nerve endings leading to anaesthesia in the lesion. The granuloma may involved peripheral nerve trunks causing enlargement a diagnostic point in all types of leprosy. In addition nerve trunk damage leads to anaesthesia and/or motor nerve damage, muscle wasting and contractures and deformities in the distribution of the nerve trunk. Examples: (i) Ulnar Nerve - Muscle wasting in hand with contracture 4th and 5th fingers with anaesthesia. Enlarged at or above Olecranon groove at elbow - may be confused with an enlarged Trochlear lymph gland adjacent to the nerve. (ii) Median Nerve - Muscle wasting and contractures thumb and 2nd and 3rd fingers. Enlarged at anterior wrist but difficult to distinguish from adjacent tendons. (iii) Radial Nerve - Wrist drop - not common.  An enlarged radial cutaneous nerve may be palpated at the lateral border of the radius proximal to the wrist. This nerves passes to the dorsum of the hand. (iv) Lateral or External Popliteal Nerve - Foot drop. May be palpated crossing the neck of the fibula. Can often be palpated in a normal muscular person. (v) Posterior Tibial Nerve - Posterior and inferior to the medial malleolus. (vi) Great Auricular Nerve - A sensory skin nerve which crosses the sternomastoid muscle in the neck. Cannot be palpated in a normal person usually. (vii) Skin Sensory Nerves near skin lesions may be enlarged. (viii) 7th Facial Nerve - Not palpable but damage to nerve leads to facial paralysis and lagophthalmos. (ix) 5th Cranial Nerve Sensory Fibres - If damaged cause anaesthesia of cornea. 1.3 Tuberculoid Borderline Leprosy (TB type) More lesions, margins less well defined and may have earlier nerve damage. Similar to Tuberculoid leprosy but with some features suggestive of Borderline leprosy. Usually skin smear negative. 1.4 Borderline Leprosy (B type) Skin lesions often large with wide erythematous raised margins. Outer margins not well defined but inner margins and central healing area well defined or "punched out". Nerve damage often prominent and beware of 7th cranial nerve damage. Borderline leprosy may be unstable and subject to "reversal" or type I reactions. Lesions may swell and nerve damage may rapidly appear. Reversal reactions are believed to be associated with an increase in cell mediated immunity or an increase in delayed type hypersensitivity, steroid treatment may be essential. Type I reaction may be difficult to distinguish from relapse when new lesions appear. Borderline leprosy usually has a low positive skin smear. 1.5 Borderline Lepromatous Leprosy (BL type) Has features of Borderline leprosy but with more general skin infiltration may start as Borderline leprosy which "downgrades" towards the lepromatous type. Nerve damage and deformities found and skin smears positive. May have ENL reactions. 1.6 Lepromatous Leprosy (L type)  Some 20% of cases are from this type. The incubation period is longer (up to 10 or more years). In general, the progress of the disease is slow and the treatment more prolonged. Skin lesions start as very vague erythematous or hypopigmented macules often on the lower back, without itch, pain, or at the beginning anaesthesia. Lesions are best seen in natural sunlight shining from the side. Skin smears positive. As the condition progresses the skin becomes more infiltrated and after some time plaques and nodules appear. The eye brows may be lost and after some years peripheral nerve damage with deformities is found. The condition may later lead to a nasal collapse and iritis with eventual blindness. Mycobacterium leprae is found in the nasal mucous membrane which may have ulcers and with secondary infection develop nasal cartilage and bone damage leading to nasal collapse. Nasal discharges are a source of infection. In addition M leprae may be found in the iris leading to blinding iritis and the organism can also cause orchitis. The histology of lepromatous leprosy is very different to the tuberculoid type. What is seen is an infiltrating granuloma of "foam" cells filled with organisms. The cells appear with clear or "foamy" intracellular areas and originate as macrophages. Lymphocytes and other cells are seen and nerve damage by the granuloma is found. Erythema Nodosum Leprosum (ENL) or type II reaction may be a problem in lepromatous or BL leprosy and is believed to be an antigen antibody immune complex condition and is histologically a vasculitis or panniculitis. Crops of red painful papules appear most often on the thighs and upper arms but can be widespread and in nerves or the iris. Can be severe with fever and ulceration and confused with typhus or other causes of a pyrexia of unknown origin. May have swelling of hands and feet or joints. May need steroids and with the use of clofazimine (Lamprene) the incidence is low. 1.7 Primary Neuritic Leprosy Enlarged nerves and nerve damage without skin lesions. Rare in HK. 2. DIAGNOSIS To make a diagnosis of leprosy at least one of the following must be found : 2.1 Typical skin lesions with anaesthesia in the lesion. Beware of facial lesions which may not show anaesthesia and of anaesthesia caused by other forms of peripheral neuritis e.g. diabetes or scar tissue. 2.2 Enlarged peripheral nerves Examples are the Ulnar nerve at elbow, radial sensory branch at wrist or great auricular nerve in neck. In leprosy the nerve will often feel harder, irregular or have tenderness (neuritis). There is considerable individual variation in the size of nerves and it is difficult to confirm enlargement at times. Hand, foot and facial deformities alone are not diagnostic of leprosy and may be caused by trauma, cervical spine disease and other conditions. 2.3 Positive Skin Smears for M leprae Not easy to do and require experience and training. The smear should have no blood in it. The reading of smears takes experience and training also. With the microscope the organisms are counted and expressed as a Bacteriological Index (log) of 0 to 6. In addition the % of viable organisms can be estimated as a Morphological Index. Skin smears help in diagnosis, monitor progress with treatment and confirm relapses. ZN stain used. Smears are taken from lesion margins, earlobes, eyebrows or back of fingers. Skin smears are taken from 6 sites in patients and 4 sites in contacts. The smears are done yearly or in the case of long term cases every 18 months. The skin is lightly pinched to prevent blood staining of the specimen and a shallow incision made with a scalpel blade. Tissue fluid or lymph is removed with the blade and placed on a slide. The Ziehl-Neelsen staining method is used (as in Tuberculosis). Bacteriological Index (BI) The Ridley logarithmic scale is used and ranges from zero to 6 and is based on the number of bacilli seen in an average microscopic field of the smear using an oil immersion objective. The 6 smears are read and averaged to give the BI. Morphological Index (MI) The percentage of live bacilli. Organisms which appear as regular rows are taken as live and organism which are irregular uneven or broken are taken as dead. When the MI is zero patients are non-infectious as is confirmed by research using animals (mice). Even without treatment the MI is not often higher than 30%. 2.4 Histology In Lepromatous leprosy, using the correct stains, the histology and organisms are typical, but Tuberculoid leprosy can be confused with skin tuberculosis. In Tuberculoid leprosy histology, nerve involvement should be seen. 3. DIFFERENTIAL DIAGNOSIS If the four diagnostic points mentioned in the previous section are followed a diagnosis can usually be made. If there is doubt the case can be observed for some months and leprosy confirmed or excluded. Leprosy seldom causes itching. 3.1 Macular Lesion Usually lack of anaesthesia and negative skin smears will differentiate vitiligo, pityriasis versicolor, pityriasis alba and other hypopigmented lesions. 3.2 Infiltrated Lesions Lack of anaesthesia or enlarged peripheral nerves as well as appearance and history will usually exclude leprosy. The various forms of skin tuberculosis including erythema induratum can be confused with leprosy as the histology can be very similar. The clinical appearances of granuloma multiforme, sarcoidosis and fungi can be similar to leprosy. 3.3 Nodules and Plaques Some forms of syphilis, skin leukaemia, mycosis fungoides and neurofibromatosis can be similar to leprosy. 3.4 Sensory Nerve Damage and/or Muscle Wasting Primary amyloidosis and Dejerine Sottas disease (a familial hypertrophic polyneuropathy) can present with enlarged peripheral nerves but are rare. Congenital sensory neuropathy can also be confused with leprosy. Diabetic neuropathy, other forms of peripheral neuritis and traumatic nerve damage need to be excluded. Cases of cervical spine disease, cervical rib and syringomyelia and motor neurone disease have been seen. Another condition seen a number of times is Bernhardt's syndrome, a friction neuritis of the lateral femoral cutaneous nerve. Such patients complain of anaesthesia in the lower lateral thigh. There are a number of possible causes of facial nerve paralysis apart from leprosy. 3.5 Neurotrophic Foot Ulcers  Diabetes should be excluded. Some patients may have other neurological diseases Raynauds disease or peripheral vascular disease. 3.6 Neurotrophic Ankle and Feet Joint Changes (Charcot Joints) Other causes need to be excluded e.g. Syphilis. 4. TREATMENT Treatment is more than anti-leprotic agents and includes plastic and orthopaedic surgery, ulcer dressings, physiotherapy, occupational therapy and attention to rehabilitation and health education. 4.1 Multidrug Therapy (MTD) World Health Organisation Regimen Patients are divided into smear negative paucibacillary (mainly Tuberculoid and BT types) and smear positive multibacillary (mainly lepromatous, BL and B types) groups. 4.2 Paucibacillary Leprosy Tab Dapsone 100 mg daily for 6 months or Inj 400 mg weekly Caps Rifampicin 600 mg monthly (or 4 weekly) for 6 months supervised As skin lesions often still remain after 6 months of treatment, dapsone is continued until inactivity and patients then observed for several years. Patients are reluctant to stop treatment if they still have skin lesions. With the 6 months treatment some later relapse but with the above method so far there has been no relapses of paucibacillary cases in HK. 4.3 Multibacillary Leprosy Tabs Dapsone 100 mg daily Caps Lamprene 300 mg weekly partly supervised Caps Rifampicin 600 mg months (or 4 weekly) supervised Taken for a minimum of 2 years or until smear negative. The treatment is continued until skin inactivity. Patients are reluctant to stop treatment until their skin is completely cleared. So far MDT trials for multibacillary leprosy show that some "persister" organisms remain and some patients relapse but trials are not fully completed. Relapse rates so far reported are low. In HK the conservative treatment of continuing Dapsone after stopping Lamprene and Rifampicin has been used with good results. Multidrug therapy was started in HK in 1977 and so far no patients who took the therapy properly have relapsed. Patients dating from the 1950's, 1960's took various monotherapies (Dapsone and other now obsolete drugs). Some later took Rifampicin. Tuberculoid and Tuberculoid/Borderline type patients have been discharged but surveillance of other types of these old patients is continued with skin smears every year or 18 months and some still take Dapsone. The number of such patients who relapse is about 3 per year (0.1% per year). Such patients who relapse are nearly all individuals who have been lost to control or have a history of poor treatment compliance. Relapsed patients are given MDT. Relapse may be confused with reversal reaction or even ENL. Low dose dapsone, gradual build up of dapsone and stopping of dapsone during reactions are no longer recommended as resistant organism may appear. 5. PROBLEMS 5.1 Dapsone A safe drug and has been given to very large numbers of patients worldwide with few serious side effects. In the past Dapsone resistant M leprae organisms were a problem but the introduction of MDT to manage this problem has been effective. Skin sensitivity may be seen or other forms of intolerance but are not common. 5.2 Lamprene Resistance is rare. The main problem is skin pigmentation and sometimes gut irritation. 5.3 Rifampicin There are reports of quite a few side effects especially with daily dosages. With Rifampicin 600 mg monthly little trouble has occurred. Resistance to Rifampicin is reported in somecountries. The antibiotic should not be used as a monotherapy and should be given under supervision, urticaria, skin rashes, haematological problems have been seen. May inhibit other drugs and caution advised in pregnancy. Bactericidal in 1 or 2 days so patient isolation is not essential or needed. When MDT is taken properly the results are very good. Patient compliance with treatment can be a problem and health education is helpful. 6. REACTIONS 6.1 Type I Reaction (reversal reaction) There is some doubt about the use of Lamprene in this condition but experience is that it may help at times. Steroids are usually needed and in the clinics Cortrosyn (ACTH) is used and is effective. Do not stop Lamprene, dapsone or rifampicin, beware of nerve damage e.g. facial paralysis. 6.2 Type II Reaction (ENL) The use of Lamprene which is anti-inflammatory reduces the incidence and is a good treatment. The dose may need to be increased to up to 200 mg daily or even 300 mg daily for a short time under close supervision. Steroids or Cortrosyn may be needed. Beware of steroid dependency and side effects e.g. peptic ulcers, moon face etc. Some patients have taken high doses of steroids before they reach our clinics. Leprosy patient have been seen on steroids who had prior incorrect diagnoses of periarteritis nodosum, panniculitis and SLE. 7. ULCER DRESSING Treatment and dressings are provided for a number of patients with neurotrophic ulceration which may be compounded by deformities and blindness. Some patients have stasis ulceration and 'mossy' growths related to lymphatic problems. Walking foot plasters often are effective. Physiotherapy to improve function is provided and essential before and after tendon transfer surgery. Patients needing surgery are referred to Orthopaedic and Plastic Surgery units and those with eye, ENT or other problems referred to relevant units. Some patients have leg amputations and need help at times with prosthetic repairs or renewals. Home helpers and Community Nurses assist some patients at home. Staff teamwork is an important point in leprosy treatment. 8. REHABILITATION Apart from the above aspects of physical rehabilitation a medical social worker assists with obtaining housing for homeless patients, job placement and welfare payments. 9. STIGMA Ancient worldwide fear and rejection of patients by society, families and individuals. Often expressed as fear of infection but probably based on the mutilating deformities, ulceration and blindness seen in advanced untreated patients. Patients may face considerable employment, housing and family problems because of leprosy stigma. The patient may react with denial of the disease, depression, inferiority feelings or may try to hide or travel to another country for treatment. Health education for the patient and family may be very helpful. 10. RESEARCH In time a reliable diagnostic blood test may become available or a preventive immunisation. Antibiotics are under trial in other countries to improve treatment and at present (1993) Ofloxacin and Minocycline are candidates. 11. PRACTICAL PROCEDURES Each new patient has a history taken, examination documentation, a skin smear, chest X-ray (for possible tuberculosis but now not very common), VDRL (may be biologically false positive in lepromatous leprosy) at times a case of latent syphilis is found, complete blood picture including Hb, WBC and reticulocyte count and any other indicated investigations or skin biopsy. The patient and family is interviewed by health nurses and health education given. Each new patient has a home visit by health staff and contacts are examined in the clinic and skin smear taken. When the index case is a tuberculoid type smear negative patient their contacts are followed up yearly until the index case is discharged. When the index case is a smear positive type of case, their contacts are usually followed up for 10 years from when the patient becomes smear negative. Attention is given to any foot ulceration, deformities, necessary physiotherapy and to social problems. Some patients have housing, job and financial or family problems. The first day that a patients attends our clinic is very important for the patient to receive careful attention for his or her problems and to have a good impression of our service. All treatment is confidential. Staff teamwork in leprosy control and treatment is important.