Mycobacterium tuberculosis was discovered by Robert Koch in 1882, while he was working in the Imperial Health Office, Berlin, Germany. This acid-fast bacillus is spread by airborne infection (or from infected cows in the case of bovine tuberculosis). There are three routes of primary infection:
• direct spread to lungs;
• from tonsils to the lymph nodes of the neck where an abscess may form and track round the edge of the sternomastoid muscle, producing a collar-stud abscess;
• from lower ileal infection to the lymph nodes of the ileocaecal angle.
The bacterium, which produces no pigment, grows well at 370C and may be seen, if there are very many organisms, in the Ziehl—Neelsen stained smear. Growth of the bacteria takes 6 weeks; thus sensitivities to the antituberculous drugs will be delayed. Recently, new techniques — including the polymerase chain reaction (PCR) — have given hope that more rapid diagnosis will soon be possible.
For the accounts of the manifestations of this disease in various organs as applied to the practice of surgery, the reader is referred to the appropriate chapters of this book.
Guidelines for treatment
Nutrition and hygienic living conditions are still crucially important in preventing the spread of this infection.
Treatment with triple therapy consisting of rifampicin 600 mg, isoniazid 300 mg and pyrazinamide 1500—2000 mg per day given orally for at least 2—3 months is the standard chemotherapy at present, followed by 6 months of double therapy (rifampicin plus isoniazid). Sensitivity testing is usually available at the end of the first period of triple therapy and, if the source of the infection is with an organism that is rests-rant to one of these drugs, appropriate changes can then be made. Ethambutol may be of use in resistant cases. In cases of pulmonary tuberculosis, the sputum should be examined to assess progress every month until the smears are negative, but should the number of acid-fast bacilli increase or the cultures remain positive, the development of resistance or noncompliance of the patient with treatment should be considered.
Genitourinary and orthopaedic tuberculosis is usually effectively treated by the standard 9-month course but the use of pyrazinamide with rifampicin and isoniazid may be required. All of these antituberculous drugs have side effects which may require repeated careful assessment and control; isoniazid causes a peripheral neuritis, ethambutol produces visual impairment and rifampicin is hepatotoxic. Pyrazinamide should be avoided in patients with gout.
It should be remembered that it is nigh impossible to eradicate every tubercle bacillus from the body. Lying dormant and enveloped in fibrous tissue, any remaining bacilli are still able to cause a flare-up of the disease, particularly after trauma, after gastrointestinal operations resulting in nutritional deficiency, and in old age, immune deficiency or long-term use of steroids. Of great concern recently is the appearance of multidrug-resistant tuberculosis (MDRTB). This has arisen as a result of poor compliance with treatment. Although there are some drugs available to treat these strains, patients with underlying immunosuppression often fail to respond and this means that the disease is now a serious threat among patients with human immunodeficiency virus (HIV) infection. Several outbreaks have been described among acquired immunodeficiency syndrome (AIDS) sufferers and a number of healthcare workers has also been infected. Drugs that may be useful in the treatment of MDRTB include ethionamide, ofloxacin, capreomycin and cycloserine.
‘Slow-growing’ opportunist mycobacteria may be found producing lesions similar to M. tulerculosis in susceptible patients. Thus, M. kansaslii is a slow-growing opportunist mycobacterium which may cause pulmonary lesions. Mycobacterium chelonaeland M. fortuitum occasionally cause subcutaneous abscesses following skin trauma. This group should always be remembered in the differential diagnosis of subcutaneous abscesses associated with skin traumas or injections (e.g. tetanus immunisation). Skin granulomas in swimmers may be caused by M. marinum, while the surgically important Buruli ulcer occurring in East Africa, which affects the exposed surface of the limbs, is caused by M. ulcerans, and presents as a spreading granulomatous nodule which subsequently breaks down and forms an ulcer. Incision of the nodule at an early stage and treatment with rifampicin may prevent an ulcer forming, but secondary infection of a Buruli ulcer may result in fibrosis and considerable deformities of a limb as a result. Mycobacterium avzum-zntracellulare is becoming increasingly recognised as a pathogen in patients with AIDS. All of the opportunist mycobacteria should be cultured to assess their sensitivity to the antimycobacterial drugs.
Leprosy (Hansen’s disease)
Gerhard Hansen first showed that leprosy was a bacterial infection caused by M. leprae. Because of the stigma attached to leprosy, Dr R.G. Cochrane and others recommended that it should be referred to as Hansen’s disease. There are probably from 10 to 15 million leprosy sufferers in the world today.
Leprosy is an infectious disease widely spread throughout the tropical and subtropical areas of the world. It is caused by M. leprae, an acid-fast bacillus morphologically like the
tubercle bacillus. It is mainly, but not entirely, contracted in childhood and late adolescence. While the mode of transmission regarding the portal of entry of M. leprae is not known, the source of infection is mainly from the nasal secretions of patients with lepromatous leprosy and not from their skin. Leprosy is no longer endemic in northern Europe, as it was in the Middle Ages, and in Norway until the late nineteenth century; neither is it now spread by immigrants in Europe. These facts suggest that leprosy requires for its transmission some factors associated with poverty or lack of hygiene that are common in the areas where it is still endemic. A vast change in the outlook for this disease has occurred in the last 30 years. The condition was formerly regarded as hopeless, but in spite of the fact that it is no’.y curable, only 25 per cent of the cases of this widely spread disease are under treatment. It is probably true to say that leprosy causes more paralysis, deformity and misery than any other disease, but that, in many cases, these could now be prevented by modern therapy, given an adequate service for early diagnosis.
Although leprosy is a systemic infection, it presents predominantly as an infection of the skin, upper respiratory tract and dermal and peripheral nerves. Leprosy must always be considered in a patient presenting with a combination of skin and neural disorder, particularly because of the variation in the preponderance of these two manifestations and the tremendous variation in the appearance and histopathology of the dermal lesions among individual patients with leprosy. These diverse manifestations led to a plethora of classification systems until Ridley and Jopling found that there was a spectrum of disease in leprosy determined by the resistance of the host . The spectrum ranges from polar lepromatous (LL) to polar tuberculoid (TT) leprosy, denoting patients with minimal and maximal irreversible capacities to mount an immunological response against M. leprae. The majority of patients is more labile in having some residual immunological capacity against M. leprae, and thus are represented as borderline (BB), or borderline lepromatous (BL) or borderline tuberculoid (BT), if they veer more
towards lepromatous or tuberculoid leprosy. If left untreated, patients anywhere within the borderline spectrum can deteriorate towards lepromatous leprosy, whereas under treatment they will shift towards polar tuberculoid leprosy.
There is little or no resistance, the bacilli multiply with little cellular response, until the subcutaneous tissues may be loaded with masses of bacilli, many of them distending macrophages as large ‘globi’. The cellular infiltrate is mainly of macrophages with a few lymphocytes.
There is a strong tissue response, the bacilli are not numerous and are seldom seen except by special concentration methods. The histology consists of an epitheloid granuloma, many lymphocytes and a few giant cells.
Characteristically, tuberculoid leprosy causes sharply localised lesions often affecting only one part of the body, while lepromatousleprosy is symmetrical and extensive. Since the damage in leprosy is mainly due to the response of the host cells, tuberculoid leprosy causes early, severe but localised deformity, while lepromatous leprosy causes deformity late, and more mildly and widely spread. The most severely deformed patients are those affected by some of the borderline forms where the disease may be both widespread through the body and also rather violent in its reactions.
A unique feature of the disease is its predilection not only for the surface of the body, but also for the cool part of the surface. Warm areas such as the axilla and gluteal cleft are spared, while the parts of the upper respiratory tract, such as the lining of the nose, are severely involved. The testis is affected, while the ovary, and other deeply placed glands and organs, are unaffected. Since leprosy does not affect the vital organs of the body, it rarely causes death, and patients do not even feel ill for most of the time they have the disease.
During treatment, many patients manifest acute episodes, which are referred to as ‘reactions’, of which there are two distinct types.
1. The ‘lepra or type I reaction’ occurs in the borderline form of leprosy (BT, BB and BL), in which the skin lesions become erythematous, warm to touch and may break down, and the nerves swell and become painful and tender to touch. It is usually caused by a rapid increase in cell-mediated immunity by the host with an outpouring of lymphocytes into the lesions giving rise to acute inflammation with associated oedema. For this reason, the lesions have been referred to as ‘reversal reactions’, advantageous by resulting in destruction of M. leprae, but causing irreversible destruction of axons when the inflammation and oedema occur in nerves.
2. The other type of reaction is referred to as erythema nodosum leprosum (ENL or type 2 reaction), usually occurring during treatment, but confined to patients with lepromatous type leprosy (BL, LL). Here there are no changes in the established leprosy lesions, but new crops of very small erythematous lesions in the skin appear associated with systemic symptoms such as malaise, fever and nerve and joint pain. Occasionally, rhinitis, acute iridocyclitis, swollen and tender lymph glands, acute epididymo-orchitis and proteinuria occur. This is an Arthus-type reaction, due to the deposition of immune complexes in and around blood vessels, locally or generalised throughout the body, and more akin to chronic serum sickness. This reaction may come and go or be persistent, and can in its most severe form be fatal.
One of the most characteristic features of leprosy is its effect on nerves . Histologically, the cellular infiltrate may be seen localised around nerve fibres in and under the skin and, on clinical examination, superficial nerves such as the ulnar and posterior auricular may be
observed to be swollen and tender. The anaesthesia that results from nerve involvement is an important point in diagnosis, and is also a cause of secondary damage and deformity. Much of the loss and disfigurement of hands and feet which has always been associated with leprosy is now known to be due not to leprosy itself, but to the damage and misuse which follow loss of pain sensation.
Until 1980, dapsone (diaminodiphenyl sulphone, DDS) was the standard treatment for leprosy. The problems of DDS resistance and the inordinately long duration of therapy have led to today’s standard treatment — multidrug therapy (MDI). For multibacillary cases (which include LL, BL, BB and some BT cases), the treatment duration is 2 years or until negativity is achieved, whereas for paucibacillary leprosy (which indudes all tuberculoid cases and many BT cases) the treatment duration is 6 months or until the lesions become inactive. Rifampicin, the first bactericidal drug against M. leprae, is given in a dose of 600 mg a day for 2 days at the beginning of each month, while DDS is given in a dose of
100 mg daily. This two-drug regimen is adequate for paucibacillary cases. For multibacillary leprosy clofazimine at 50 mg daily is added as the third drug. Recently, clarithromycin, ofloxacin and minocycline have been shown to be effective.
For reactions, symptomatic treatment, including analgesics, is given for milder cases. Evidence of nerve damage indicates a necessity to start steroid therapy. For the more severe reactions, reversal and ENL, it is absolutely essential to treat with steroids to protect the nerves and to keep the patient going. In ENL reactions, but only in LL cases, thalidomide has proved to be very beneficial and is also useful in the treatment of steroid dependency. Thalidomide, if available, is used to treat only male patients, or females outside the childbearing years,because of its known teratogenic effects. Psychotropic drugs, e.g. chlorpromazine and amitriptyline, are often needed in cases of severe reaction to treat associated psychological disturbances.
Decompression of nerves
The relief of compression caused by the thickened nerve sheath and by the fibrous roofs of tunnels at entrapment sites (cubital, carpal and tarsal tunnels) is an important supplementary procedure to prevent further damage to the involved peripheral nerve trunks. Intractable pain is a definite indication, while increasing paralysis, in spite of treatment with steroids, is a further indication for nerve decompression.
The deformities of leprosy are divided into primary — those which are caused directly by leprosy and its reactions and secondary — those which result from anaesthesia and consequent misuse. The stigma of leprosy is the stigma of deformity, and a wide-open field awaits the plastic surgeon in this disease.
The face. Primary deformity. The skin of the face becomes thickened and sometimes nodular in lepromatous leprosy ; the forehead, cheeks, nose and ears are especially affected. The result in the acute phase is referred to as leonine facies’. This infiltration subsides under medical treatment, but may leave the skin wrinkled and without its normal support, producing, in a younger person, a caricature of old age. The hair of the eyebrows falls out and the lateral cartilages and septum of the nose may be destroyed, leaving collapse of the centre of the nose and lifting of the tip towards the bridge . The upper branches of the facial nerve may he paralysed, giving rise to lagophthalmos; the lower branches are sometimes partially paralysed.
Patients with the above deformities usually find it quite impossible to return to normal social relationships even though their leprosy may be cured. Plastic surgery can completely transform such faces using a postnasal inlay to the nose and an ‘island flap’ for the eyebrows. A temporalis muscle segment reactivates the eyelids and a facelift may restore more normal contours to the skin.
Eyes. Some of the blindness of leprosy is simply due to exposure following paralysis of the eyelids. This is correctable by plastic surgery. Other causes of loss of vision are lepromatous infiltration of the anterior segment of the eye and acute allergic changes of the tissues associated with reaction. Acute iridocyclitis is one of the commonest manifestations of this allergic reaction. Any redness of the eye or loss of visual acuity in leprosy demands full examination and prompt treatment if the sight is to be saved. Treatment should include atropine and hydrocortisone eyedrops as well as oral steroids
Hands . The work on reconstruction of the hand in Hansen’s disease was started by Professor Paul Brand.
Primary deformity. In the upper limbs, leprosy causes paralysis, frequently in the ulnar nerve at the elbow and in the median nerve at the wrist but rarely in the motor part of the radial nerve (I per cent).
Treatment.The extensor carpi radialis hrevis muscle is extended into the hand with free grafts which run along the lines of the lumbrical tendons to correct the clawing of the fingers. The flexor sublimis tendon to the ring finger is withdrawn in the forearm and rerouted to oppose the thumb along the line of the abductor hrevis. In this way the fingers and thumb may be balanced and function almost normally. Before attempting operation it is important to make sure that the fingers are made mobile by massage and exercise.
Secondary deformity. Since the hand is often totally anaesthetic, patients frequently burn or damage themselves by the uninhibited strength which they use through their fingertips. Their hands become scarred and progressively absorbed until only stumps remain. It takes patience and perseverance to teach patients that their hands can be preserved only by constant alertness to foresee possible dangers, and constant gentleness to their own tissues which are not protected by pain. Once they are convinced that it is not leprosy that is destroying their fingers, they may he willing to accept the discipline of caring for themselves.
Feet. Primary deformity. In the lower limbs, the posterior tibial nerve is often involved at the ankle, giving rise to ‘clawing’ of the toes and anaesthesia of the sole of the foot. The lateral popliteal nerve may also be destroyed, giving rise to footdrop. The medial popliteal nerve is never involved, so the tibialis posterior muscle can be safely used to correct footdrop.
Secondary deformity. The anaesthesia of the sole of the foot is very serious because almost every patient with insensitive feet sooner or later develops trophic ulceration. If patients then continue to walk on their ulcers, the condition progresses and the infection spreads until, after a few years, the foot is contracted and distorted, and destroyed to the point where amputation must be advised.
It is important for patients to understand the pathology of their ulcers and to realise that they are not due directly to leprosy. These ulcers heal readily with rest in a plaster cast and their recurrence can be prevented by the regular use of special footwear designed to spread the weight evenly over the whole foot.
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