Tuberculoid leprosy (TT)
In tuberculoid leprosy the infection is localized because the patient has unimpaired cell-mediated immunity. The characteristic, usually single, skin lesion is a hypopigmented, anaesthetic patch with thickened, clearly demarcated edges, central healing and atrophy. The face, gluteal region and extremities are most commonly affected. Frequently the nerve leading to this hypopigmented patch and the regional nerve trunk are thickened and tender. Unlike other parts of the body, a tuberculoid patch on the face is not anaesthetic. Nerve involvement leads to marked muscle atrophy. Tuberculoid lesions are known to heal spontaneously.
Borderline-tuberculoid (BT) leprosy Resembles TT but skin lesions are usually more numerous, smaller and may be present as small ‘satellite’ lesions around larger ones. Peripheral but not cutaneous nerves are thickened, leading to deformity of hands and feet. Borderline (BB) leprosy Skin lesions are numerous varying in size and form (macules, papules, plaques). The annular, rimmed lesion with punched out, hypo pigmented anaesthetic centre is characteristic. There is widespread nerve involvement and limb deformity.
Borderline-lepromatous (BL) leprosy There are a large number of florid asymmetrical skin lesions of variable form, which are strongly positive for acid-fast bacilli. Skin between the lesions is normal and
often negative for bacilli. Lepromatous leprosy (LL) Although practically every organ can be involved, the changes in the skin are the earliest and most obvious manifestation. Peripheral oedema and rhinitis are theearliest symptoms. The skin lesions predominantly occur on the face, the gluteal region and the upper and lower limbs. They may be macules, papules, nodules or plaques. Of these, the macule is the earliest lesion. Infiltration is most noticeable in the ear lobes. Thinning of the lateral margins of the eyebrows is characteristic. The mucous membranes are frequently involved, resulting in nasal stuffiness, laryngitis and hoarseness of the voice. Nasal septal perforation with collapse of the nasal cartilages produces a saddle-nose deformity. With progression of the disease, the typical leonine facies due to infiltration of the skin becomes apparent. Glove and stocking anaesthesia, gynaecomastia, testicular atrophy, ichthyosis and nerve palsies (facial, ulnar, median and radial) develop late in the disease. Neurotrophic atrophy affecting the phalanges leads to the gradual disappearance of fingers. Nerve involvement is less pronounced than in TT.
LUCIO’S PHENOMENON is seen only in Mexico and Central America, where LL is associated with an endarteritis which results in skin ulceration. The ulcers are large, with undermined edges and markedly necrotic bases. Smears from the base generally reveal numerous acid-fast bacilli. Healing is by scar formation. Treatment is wide surgical excision with skin grafts. Chemotherapy alone is ineffective in healing ulcers. The lepromin test This is a measure of host resistance to leprosy and not a test for detecting leprosy: 0.1 ml of a suspension of dead bacilli (either Mitsuda lepromin or the Dharmendra lepromin) is injected intradermally. Two reactions are observed:
1 The early Fernandez reaction becomes positive in 48 hours and reflects the sensitivity of the tissue to the leprosy bacilli protein.
2 The late (Mitsuda) reaction develops in 4-5 weeks and reflects the resistance of the host to the bacteria. This reaction is strongly positive in TT and is negative in LL.
Lepra reactions are immunologically mediated acute reactions that occur in patients with the borderline or lepromatous spectrum of disease. Two forms are recognized.
ERYTHEMA NODOSUM LEPROSUM (ENL; type II lepra reaction) is a humoral antibody response to an antigenantibody complex (i.e. a type III hypersensitivity reaction). It is seen in 50% of patients with treated LL. It is characterized by fever, arthralgia and crops of painful, subcutaneous erythematous nodules, iridocyclitis and other systemic manifestations. It may last from a few days to several weeks.
THE BORDERLINE REACTION (type I lepra reaction) is seen following treatment of patients with borderline disease; it is a type IV delayed hypersensitivity reaction. Both upgrading or reversal reactions (i.e. a clinical change towards a more tuberculoid form) and downgrading reactions (i.e. a change towards the lepromatous form). can occur. The borderline reaction is characterized by acute inflammation of pre-existing borderline lesions. Neurological deficits such as an ulnar nerve palsy may occur abruptly.
The diagnosis of leprosy is essentially clinical. Patients should be examined in adequate natural light. The demonstrationof acid-fast bacilli in smears from the skin or nasal mucosa is highly suggestive. Occasionally nerve biopsies are helpful. The definitive diagnosis is established by cultivating the organisms in the foot-pads of mice. Detection of M. leprae DNA is now possible in all forms of leprosy using the polymerase chain reaction and can be used to assess the efficacy of treatment.
Leprosy should be treated in specialist centres with adequate physiotherapy and occupational therapy support. Multidrug therapy is now essential because of developing drug resistance (up to 20% of cases are resistant to dapsone).
Dapsone (di-amino-di-phenyl sulphone, DDS), a folate synthetase inhibitor, is bacteriostatic. It has the advantage of being cheap and well tolerated. Side-effects are few and include haemolytic anaemia and sulphaemoglobinaemia. In 1982 the World Health Organization recommended that for multi-bacillary forms of leprosy (BB, BL and LL types) it should be taken on a daily basis (100 mg) along with rifampicin 600 mg once monthly and clofazimine 50 mg daily with an extra dose of 300 mg monthly. The monthly doses are given under supervision. This triple therapy should be given for a minimum of 2 years or continued until a patient’s skin smears become negative for acid-fast bacilli. However, in paucibacillary forms (TT or BT) 6 months’ therapy with DDS 100 mg daily and rifampicin 600 mg monthly is recommended. The major disadvantage with clofazimine is that it is a dye and causes a generalized reddish-brown pigmentation in light-skinned individuals and a slate grey pigmentation in dark-skinned individuals. Ethionamide is a suitable alternative. Acedapsone (DADDS), a depot sulphone, has been used with some success. Surgery and physiotherapy play an important role in the management of trophic ulcers and deformities of the hands, feet and face.
Treatment of lepra reactions
Treatment of lepra reactions is urgent, as irreversible eye and nerve damage can occur with amazing rapidity. Antileprosy therapy must be continued. Type II lepra reactions (E L) are effectively treated with analgesics, chloroquine, clofazimine and antipyretics. Thalidomide, a drug known for its potent teratogenic effects, is by far the most effective in the ENL reaction, but must be used with caution. Prednisolone 30-40 mg daily for a few weeks is effective in type I reactions.
PREVENTION AND CONTROL
This depends on rapid treatment of inf~cted patients, particularly those with LL and BL, to decrease the bacterial reservoir. It is spread by close contact, but only a small proportion of contacts-approximately 1%-develop the disease. Antileprosy vaccines are under clinical trial; the efficacy of the BCG vaccine against leprosy is debatable. Mass chemoprophylaxis is impracticable and its efficacy in household contacts has not been established. Mycobacterial ulcer Also known as Buruli ulcer, after the Buruli region in Uganda, this condition occurs in tropical, rural areas near rivers, e.g. in Zaire, igeria and Malaysia. It is caused by M. ulcerans. The disease is contracted by swimming in infected water. Initially a small subcutaneous nodule develops. This undergoes ulceration that involves the subcutaneous tissue, muscle and fascial planes. The ulcers are usually large, with undermined edges and markedly necrotic bases. Smears taken from necrotic tissue generally reveal numerous acid-fast bacilli. Treatment is wide surgical excision with skin grafts. Antituberculous therapy is ineffective.