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:
• 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
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 chelonael
and 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 (Fig. 8.1). 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.
Lepromatous
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.
Tuberculoid
leprosy
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 lepromatous
leprosy 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 (Fig. 8.2). 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,
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.
Surgery
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 (Fig. 8.3); 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 (Fig.
8.4).
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 (Fig.
8.4)
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
(Fig. 8.5). 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 (Fig.
8.2) 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
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.