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Essentials
©f Leprosy
ALL AFRICA
LEPROSY
AND
REHABILITATION
TRAINING
CENTRE,
ADDIS ABABA,
ETHIOPIA.
ESSENTIALS OF LEPROSY
(3rd Edition)
Edited by
J. M. H. PEARSON
and
W.WHEATE
H.
Published by the
ALL AFRICA LEPROSY AND REHABILITATION
TRAINING CENTRE
(ALERT)
Printed by
RAKSHABANDHU TRUST
(friend of the physically handicapped)
Besantnagar, Madras-600 090. India
— 1979 —
CONTENTS
Foreword
1.
Introduction
1.1 Definition
1.2 History
2.
Epidemiology
2.1
2.2
2.3
2.4
2.5
Distribution
influence of sex
Influence of age
Source of infection
Mode of transmission
2.5.1 Route of exit
2.5.2 Route of entry
2.5.3 The "bridge"
2.6 Susceptibility
2.6.1 Factors influehcing susceptibility
2.6.2 Factors influencing type of leprosy
3.
5.
6.
Bacteriology and Experimental Leprosy
Definitions
3.1.1 The Bacterial Index (Bl)
3.1.2 The Morphological Index (Ml)
3.2 Experimental leprosy in mice
3.2.1 Multipiication time of M. leprae
3.2.2 Viability Of M. leprae
3.2.3 Testing of new drugs
3.2.4 Drug resistant strains of m. leprae
3.3 Other animal models of leprosy
3.3.1 Immunologically deficient rodents
3.3.2 Armadillos
3.1
4.
7.
8.
Clinical Features and Classification
4.1
4.2
4.3
Subclinical infection
Indeterminate leprosy
The spectrum of "established leprosy"
4.3.1 Tuberculoid leprosy
4.3.2 Lepromatous leprosy
4.3.3 Borderline leprosy
r, it, it
0537'.
9.
leprosy
cosy
^^Siires in classification
==)f the classification
continuity
iiations in leprosy
Station of Ridley and Jopling
•classification
sses
of treatment
complications
Leprosy
Hvement
—.wolvement
Sal changes in nerves
~iion
zoisum leprosum (ENL)
■ iprosy
ii immunity
nunity
■function
n test
•ifferential Diagnosis of Leprosy
i leprosy
diagnosis of leprosy
i skin diseases
i neurological diseases
i limb deformities
if Leprosy
lable
of chemotherapy
Multiple drug therapy
esistance in leprosy
nti-leprosy drugs
3
CONTENTS
Foreword
I.
Introduction
1.1
1.2
2.
Epidemiology
2.1
2.2
2.3
2.4
2.5
2.6
3.
Definition
History
Distribution
influence of sex
Influence of age
Source of infection
Mode of transmission
2.5.1 Route of exit
2.5.2 Route of entry
2.5.3 The “bridge"
Susceptibility
2.6.1 Factors influehcing susceptibility
2.6.2 Factors influencing type of leprosy
Bacteriology and Experimental Leprosy
3.1
Definitions
3.1.1 The Bacterial Index (Bl)
3.1.2 The Morphological Index (Ml)
3.2 Experimental leprosy in mice
3.2.1 Multiplication time Of M. leprae
3.2.2 Viability Of M. leprae
3.2.3 Testing of new drugs
3.2.4 Drug resistant strains of m. leprae
3.3 Other animal models of leprosy
3.3.1 Immunologically deficient rodents
3.3.2 Armadillos
4.
Clinical Features and Classification
4.1
4.2
4.3
Subclinical infection
Indeterminate leprosy
The spectrum of “established leprosy"
4.3.1 Tuberculoid leprosy
4.3.2 Lepromatous leprosy
4.3.3 Borderline leprosy
0537:
4.4
4.5
4.6
5.
Nerve Involvement in Leprosy
5.1
5.2
5.3
6.
Cell mediated immunity
Humoral immunity
Macrophage function
The lepromin test
Diagnosis and Differential Diagnosis of Leprosy
8.1
8.2
9.
Reversal reaction
Erythema nodosum leprosum (ENL)
Immunology in Leprosy
7.1
7.2
7.3
7.4
8.
Nerve trunk involvement
Dermal nerve involvement
Histopathological changes in nerves
Reactions in Leprosy
6.1
6.2
7.
Other types of leprosy
4.4.1 "Pure neural” leprosy
4.4.2 "Histoid” leprosy
Different nomenclatures in classification
4.5.1 The purpose of the classification
4.5.2 The need for continuity
4.5.3 Regional variations in leprosy
4.5.4 The classification of Ridley and Jopling
The importance of classification
4.6.1 Problem cases
4.6.2 The period of treatment
4.6.3 The risk of complications
Diagnosis of leprosy
Differential diagnosis of leprosy
8.2.1 From skin diseases
8.2.2 From neurological diseases
8.2.3 From limb deformities
Chemotherapy of Leprosy
9.1 Drugs available
9.2 Principles of chemotherapy
9.3 Single or multiple drug therapy
9.4 Dapsone resistance in leprosy
9.5 Notes on anti-leprosy drugs
3
10.
Therapy of Reactions and Neuritis
Treatment of reversal reaction
10.1.1 Mild reversal reaction
10.1.2 Severe reversal reaction
10.2 Treatment of ENL
10.2.1 Clinical patterns of ENL
10.2.2 Treatment of episodic ENL
10.2.3 Treatment of continuous ENL
10.2.4 Anti-leprosy treatment and ENL
10.1
11.
The Eye in Leprosy
Non lepromatous leprosy
11.1.1 Lagophtalmos
11.1.2 Corneal anaesthesia
11.2 Lepromatous leprosy
11.3 Management of eye complications in leprosy
11.3.1 Permanent lagophthalmos
11.3.2 Iridocyclitis
11.3.3 Other eye complications
11.1
12.
Physical Therapy in Leprosy
12.1
12.2
13.
Exercises
Skin care
The Foot in Leprosy
The aetiology of trophic ulcers
13.1.1 Muscle paralysis
13.1.2 Bone damage
13.1.3 Anaesthesia
13.2 Management of the ulcerated foot
13.3 Principles of prescribing footwear in leprosy
13.1
14.
The Place of Surgery in Leprosy
14.1 Surgery of infection
14.2 Surgery of bone
14.3 Tendon transfer operations
14.4 Eye surgery
14.5 Surgery of nerves
14.6 Plastic surgery
14.7 Amputations
4
15.
Principles of Leprosy Control
15.1 Early detection (case finding)
15.2 Regular treatment (case holding)
15.3 Requirements of a successful control programme
16.
Principles of Rehabilitation
Preventive rehabilitation
Active rehabilitation
16.2.1 Sheltered workshops
16.2.2 Training programmes
16.3 Loss of self respect
16.1
16.2
17.
Principles of Health Education
APPENDICES
1.
2.
3.
Taking skin smears
Taking biopsies
Sensory testing
5
Foreword
This booklet is designed for doctors, medical students, and senior leprosy
workers. The first edition was published 6 years ago; the fact that this second
edition has required rewriting to the extent of becoming effectively anew
publication is an indication of rapid progress in the understanding of leprosy.
In a work such as this, which attempts in a small compass to cover the whole
field of leprosy, it is hard to maintain a due sense of proportion. This booklet
attempts to do so, but with one exception. Disproportionate space has been
allotted to the treatment of leprosy and its complications. There is sufficient
information for the doctor who is inexpereinced in leprosy to manage the
disease and most of its complications with reasonable confidence: we hope
this will encourage leprosy treatment in general hospitals.
No small book on a large subject can avoid dogmatism, and this one is no
exception. Where statements in this booklet contradict generally accepted
teaching, they have been made with careful consideration: and, particularly
in the sections dealing with therapy, the treatments advised are those in
normal use in ALERT. They have been proved safe and effective, and are also
in agreement with current World Health Organisation recommendations.
This booklet has not been copyrighted. We encourage its translation, however,
reproduction (in whole or part) in any language should include due acknow
ledgement to ALERT. ALERT would appreciate receiving copies of any trans
lations or other reprintings of any part of this book; they will be valuable for
use by trainees coming to ALERT.
We are most grateful to the staff members and others working in the Addis
Ababa Leprosy Hospital, who over the years have continued our education
in leprosy, and have contributed to and reviewed this booklet. But, as editors,
we must accept responsibility for the final text.
J. M. H. Pearson
H. W. Wheate
6
1.
11.1.
INTRODUCTION
Definition
Leprosy is a chronic infectious disease of man, caused by Mycobacterium
neprae. It affects chiefly skin and peripheral nerves: but in some forms of the
•disease m.leprae can be found in large numbers elsewhere, particularly in
the nasal mucous membrance, smooth and striated muscle, liver, spleen,
lymph nodes, eyes, testes, and blood vessel walls. Leprosy can occasionally
cause glomerulo-nephritis and polyarthritis, probably due to immune complex
deposition.
1.2
History
It is probable that the disease called leprosy in the Old Testament was not
leprosy as we know it today. Leprosy has been described in skeletons of
Egyptian mummies from the 5th Century A.D.
Moller-Christensen has demonstrated the occurence of leprosy In skeletons
unearthed from church burying-grounds associated with leprosy hospitals in
Denmark, from as early as the 12th century. Leprosy is thought to have reached
its peak in Europe during the 16th century. Endemic leprosy disappeared from
Northern Europe at the end of the 19th century, but it is still not uncommon in
Southern Spain, Southern Italy, Sicily and Malta.
Little is known of the history of leprosy in Africa. It is probable that it spread
from the Middle East along the great trade routes during the Middle Ages. It
is possible that its penetration into tropical and Southern Africa is of relatively
recent occurrence. There is some evidence, for example, that an epidemic of
leprosy occurred in the Eastern Provinces of Nigeria from the 1920's onwards.
It is possible that we are at present seeing a similar phenomenon in Ethiopia.
Leprosy is well established in the Central Highlands, but there is evidence,
both clinical and historical, that cases have only been present in significant
numbers in other parts of Ethiopia for a relatively short period.
Armauer Hansen discovered that Mycobacterium leprae was the causal
organism in 1873. In appearance the Mycobacterium is similar to Mycobac
terium tuberculosis. It has, however, not been cultured in vitro, and Koch’s
postulates have yet to be fulfilled.
7
2.
2.1.
EPIDEMIOLOGY
Distribution
Leprosy is distributed world-wide. It is estimated that there are a total of 15
million cases in the world, of whom 34 million are in Africa. Only about 25%
of the total cases are being treated. In some areas the figure is certainly
much lower than this.
2.2.
Influence of Sex
All forms of leprosy are rather more frequent in males than in females, the
sex ratio being about 2:1. In adults this difference is less marked in the form
of leprosy with few bacilli (tuberculoid leprosy); and it is absent prior to
puberty. The reason for these facts is not known, but they are generally
attributed to differences in susceptibility rather than exposure.
2.3.
Influence of Age
The idea that children are more susceptible to leprosy than adults is not
supported by the facts. The peak of . the age curve for diagnosis of leprosy
is between 15 and 25 years of age. New cases are often seen in old age. It
seems probable that all ages are more or less equally susceptible, and that
opportunities for contact, coupled with the incubation period, are the most
important factors giving rise to patterns of age at onset.
2.4.
Source of Infection
The only known source of infection is the human case. It is probable that the
more bacilliferoustypeof leprosy (lepromatous leprosy) is the principal source
of the disease, though it must be admitted that contact with such patients
often cannot be traced.
2.5.
Mode of Transmission
For transmission of leprosy to occur viable bacilli must leave the body of the
patient and enter that of the contact. Three factors therefore must be con
sidered : the rout© of exit, the route of entry, and the "bridge" between them.
The route of exit It is now well established that the usual route is the
nasal mucous secretion. It is very unusual to find leprosy bacilli on the surface
of the skin, whereas a patient with active lepromatous leprosy will excrete each
day in nasal secretions about the same number of bacilli as a patient with
open pulmonary tuberculosis will cough up in sputum.
2.5.1
8
The route of entry. It likely that the usual mode of transmission is via
droplets or dust, and the respiratory tract is the normal portal of entry. Penet
ration through normal skin seems inctrinsically unlikely, though there are a few
well documented reports of leprosy lesions at the site of needle pricks or cuts.
Inoculation by mosquitoes, scabies mites, or other insects is also possible.
2.5.2
2.5.3.The "bridge". It has been shown that, (at normal laboratory temperature
and humidity), M. leprae remain viable for at least 24 hours, and sometimes
longer. This finding makes droplet or dust-borne transmission a reasonable
hypothesis. All the known facts about the spread of leprosy can be explained
on this basis.
2.6 Susceptibility
Two separate issues must be considered here; firstly, factors that make an
individual more likely to contract leprosy; and secondly, factors that influence
the type of disease that develops.
2.6.1
Factors influencing susceptibility
There is some epidemiological evidence suggesting that certain families are
more susceptible to leprosy than average. There seems to be no evidence
that any particular race is more susceptible than another nor has leprosy been
linked to known genetic characteristics. It is probable that susceptibility is
little affected by age or nutritional status. It is possible, however, that prior
infection by some strains of non-pathogenic mycobacteria (many of which are
present in the environment) may affect susceptibility to subsequent infection
with M. leprae.
2.6.2
Factors influencing the type of leprosy
There is good evidence that more deeply pigmented races tend to develop
tuberculoid leprosy, whereas those with paler skins have a higher propor
tion of lepromatous cases. Moreover, in most races males have a higher
lepromatous/tuberculoid ratio than females.^
3.
3.1
BACTERIOLOGY AND EXPERIMENTAL LEPROSY
Definitions
M. leprae can be obtained from skin lesions
by the "slit and scrape" method
(see Appendix 1). The material so obtained is spread on a microscope slide,
stained, and examined using an oil immersion lens. Two findings are recorded:
9
3.1.1
The Bacterial Index (Bl)
This represents the average number ot bacilli peroil immersionfield, expressed
as 0 to 6 + on a logarithmic scale. It is a very approximate indication of the
total baci I lary load of the patient. The Bl falls during treatment as dead bacilli
undergo lysis and are absorbed.
3.1.2
The Morphological Index (Ml)
Even in untreated patients a considerable proportion of bacilli show irregular
staining and appear fragmented. The Ml is the percentageof uniformly stained,
solid looking ("morphologically normal") bacilli that are present. The Ml is
usually between 5 and 50 in untreated patients; it falls close to 0 after about 6
months of effective chemotherapy, the fall indicating that the bacilli have been
rendered non-viable. Bacilli appearing fragmented by light microscopy have
been shown by electron microscopy to have lost their normal appearance and
become masses of structureless cytoplasm.
3.2.
Experimental leprosy in mice
In )960 it was shown that m.leprae, when inoculated into the foot pads of
mice, produced a Iimited, microscopic infection. This model has been used for
a number of purposes:-
has been shown to be 10 - 14 days, a figure
which agrees satisfactorily with clinical evidence that the disease has an
incubation period of 2 or more years.
3.2.1 The Multiplication Time
3.2.2 The viability of M.leprae can be tested in this way. It has been shown
that when baciIli appear fragmented by light microscopy they fail to multiply
on mouse foot pad inoculation.
3.2.3 New drugs, particularly those active againstother mycobacteria, can be
screened for anti-leprosy activity. This is now a necessary preliminary investi
gation which must precede clinical trials.
strains of bacilli obtained from patients failing to respond satisfactorily
to treatment can be tested for drug resistance.
3.2.4
3.3.
Other animal models
Since 1960 a number of other animal models have been developed, of whicl
two groups are of particular importance.
10
3..'
Cti
tc
p
T
r
^^^■nunologicallv deficient rodents
occlude the thymectomised irradiated mouse, the neonatally tMH.
Lewis rat, and the "nude mouse." All these animals develop a more
^^ssive infection, which sometimes closely mimics lepromatous leprosy.
vwis rat is probably the most practical of the three These animals offer
i.al for chemotherapeutic trials, and to develop models of "reaction" in
fsss-.y.
Armadillos
——umber of di fferent species of armadillo have been shown to develop leprosy
sas severe systemic disease, which is ultimately lethal, and may be analogous
=t;ala azar rather than leprosy. These animalscan be a source of very large
Ambers of m.leprae, and are chiefly of value for this reason. They also
^'er potential for determining bacillary mutation rates for resistance to
ffferent anti-leprosy drugs.
»--igure i
The Natural History of untreated infection with
Mycobacterium
Leprae.
11
3.1.1
The Bacterial Index (Bl)
This represents the average number of bacilli peroil immersion field, expressed
as 0 to 6 + on a logarithmic scale. It is a very approximate indication of the
total bacillary load of the patient. The Bl falls during treatment as dead bacilli
undergo lysis and are absorbed.
3.1.2
The Morphological Index (Ml)
Even in untreated patients a considerable proportion of bacilli show irregular
staining and appear fragmented. The Ml is the percentageof uniformly stained,
solid looking (“morphologically normal'1) bacilli that are present. The Ml is
usually between 5 and 50 in untreated patients; it falls close to 0 after about 6
monthsof effective chemotherapy, the fall indicating that the bacilli have been
rendered non-viable. Bacilli appearing fragmented by light microscopy have
been shown by electron microscopy to have lost their normal appearance and
become masses of structureless cytoplasm.
3.2. Experimental leprosy in mice
In J960 it was shown that M.leprae, when inoculated into the foot pads of
mice, produced a limited, microscopic infection. This model has been used for
a number of purposes: -
has been shown to be 10 - 14 days, a figure
which agrees satisfactorily with clinical evidence that the disease has an
incubation period of 2 or more years.
3.2.1 The Multiplication Time
3.2.2 The viability of M.leprae can be tested in this way. It has been shown
that when bacilli appear fragmented by light microscopy they fail to multiply
on mouse foot pad inoculation.
3.2.3 New drugs, particularly those active against other mycobacteria, can be
screened for anti-leprosy activity. This is now a necessary preliminary investi
gation which must precede clinical trials.
3.2.4 Strains of bacilli obtained from patients failing to respond satisfactorily
to treatment can be tested for drug resistance.
3.3.
Other animal models
Since I960 a number of other animal models have been developed, of which
two groups are of particular importance.
10
3.3.1
Immunologically deficient rodents
These include the thymectomised irradiated mouse, the neonatally thymectomised Lewis rafjand the "nude mouse." All these animals develop a more
progressive infection, which sometimes closely mimics lepromatous leprosy.
The Lewis rat is probably the most practical of the three These animals offer
potential for chemotherapeutic trials, and to develop models of "reaction" in
leprosy.
3.3.2
Armadillos
A number of different species of armadillo have been shown to develop leprosy
as a severe systemic disease, which is ultimately lethal, and may be analogous
to kala azar rather than leprosy. These animalscan be a source of very large
numbers of M.leprae, and are chiefly of value for this reason. They also
offer potential for determining bacillary mutation rates for resistance to
different anti-leprosy drugs.
figure I
The Natural History of untreated infection with
Mycobacterium
Leprae.
11
4 CLINICAL FEATURES AND CLASSIFICATION
The natural history of untreated leprosy is shown In outline in Fig. 1
4.1
Subcllnical infection
This may be comparable to the "Ghon focus" in tuberculosis: the site of the
infection has not been identified. Exposure to leprosy in the absence of
clinical manifestation of disease can, however, be demonstrated by immuno
logical tests, which are positive in a high proportion of workers who have close
contact with patients. This is the normal response to exposure to Myco.Leprae
— the development of immunity.
4.2
Indeterminate leprosy
This consists of one or a few vague hypopigmented macules of the skin,
which may be slightly dry in texture and sweat less readily than normal. It is
very hard to find leprosy bacilli inthe lesions, and well overhalf of them resolve
without treatment, leaving the contact free of disease and immune to further
infection with leprosy.
4.3
The spectrum of "Established leprosy”
if the subject has too little ability to "contain” the infection, he develops one
of the established forms of leprosy. This may evolve from indeterminate
or arise de novo. The type of leprosy depends on the host resistance, and
is not related to strain differences in M.leprae.
4.3.1
Tuberculoid leprosy
This is characterised by the presence of rather few, well defined, hypopig
mented, lesions with completeor partial anaesthesia, which often show central
healing. The patient has high resistance, the patches enlarge slowly, and
leprosy, bacilli are very hard to find. This type of leprosy may be selfhealing, but usually should be treated.
Histologically the appearance is that of an epithelioid granuloma, with rather
dense foci of lymphocytes, and often Langhans-type giant cells. Caseation is
very unusual except In nerve trunks, and probably represents a hyperactive
immune response to a focus of leprosy bacilli that had previously been "im
munologically concealed” within the Schwann cells of the nerve.
12
4.3.2
Lepromatous leprosy
This represents the other extreme of the spectrum of host resistance, where
the patient is unable to resist the infection, and the bacilli multiply almost
unchecked. They are found in highest concentration in skin and nerves, but
are not confined to these sites. There is a bacteraemia of 10' - 107 bacilli
per ml, (in spite of which the patient seldom feels ill,) and bacilli are found in
large numbers in nasal mucous membranes, liver, spleen, lymph nodes, testes,
eyes, smooth and striated muscle, and blood vessel walls. The skin lesions
are multiple, vague, slightly hypopigmented macules, often with only slightly
impaired sensation. As the disease progresses raised lesions — plaques and
nodules — develop, and there is general infiltration of the body skin, usually
maximal in the cooler zones of the body. At later stages, extensive
anaesthesia can develop.
The histological appearance in these casesis of a rather uniform infiltration
of macrophages heavily loaded with leprosy bacilli. Lymphocytes are scanty,
though there may be many plasma cells. The "foam cell” is a degenerating
macrophage containing destroyed bacilli and lipid material. Its presence indi
cates regression of the disease, either from naturalcauses or during treatment.
4.3.3
Borderline leprosy.
Sometimes called "dimorphous leprosy”. This classification includes the large
group of patients with intermediate grades of resistance to the infection. The
appearance of the skin lesions is very variable. When the resistance is higher
(subpolar tuberculoid), they look like tuberculoid lesions, but there are too
many for the disease to be classified as polar tuberculoid. When the resistance
is lower (subpolar lepromatous) they look like lepromatous lesions, but
macules and nodules are more sharply defined, with areas of normal looking
skin between them. There is usually some asymmetry of the lesions, whereas
polar lepromatous leprosy shows complete symmetry.
In the midrange of resistance, the lesions show a mixed appearance, some
looking like tuberculoid, some like lepromatous lesions. Usually, however,
there are lesions which have very clearly defined areas of central healing
(“punched out" areas) and somewhat less well defined outer edges: these
are characteristic of the midrange of borderline leprosy.
An important point to remember when considering borderline leprosy is that
the host resistance is unstable. As untreated leprosy progresses the resistance
may collapse, and the disease drifts towardsthe lepromatous pole; this process
13
is called "downgrading". Similarly under treatment resistance can recover,
and the leprosy can "upgrade" towards the tuberculoid end of the spectrum.
When these processes occur rapidly, they may be accompanied by fever
and episodes of increased swelling and erythema of the skin lesions: these are
called "reaction".
Histologically the appearance of borderline leprosy is as variable as the
macroscopic appearance: but in any one patient the microscopic appearance
is rather uniform, even of lesions which differ macroscopically. In the mid
range of borderline leprosy the characteristic appearance is an epithelioid
granuloma with scanty lymphocytes but moderate numbers of bacilli.
4.4.
Other types of leprosy
Two types of leprosy are sufficiently distinctive to merit separate description
though they are varieties of the established groups of leprosy.
4.4.1.
"Pure neural" leprosy
The nerve trunks are damaged and usually enlarged, but no skin lesions are
visible. Nerve biopsies show that these patients usually belong to the tuber
culoid end of the spectrum.
4.4.2. "Histoid" leprosy
In this variety of lepromatous leprosy patients show very sharply demarcated
nodules (which are heavily loaded with bacilli) but relatively uninvolved skin
between. The nodules are sometimes in unusual places (eye, antecubital or
popliteal fossae, abdomen). These patients are most commonly relapsed
cases, having either stopped treatment too soon or developed drug resistance;
in addition to active nodules, they often show stigmata of old healed lesions.
It is as if the nodules had developed by the multiplication of a few surving
bacilli in a small number of skin sites.
4.5 Different nomenclatures in classification
Different nomenclatures are used to classify leprosy in different parts of the
world. The differences are accounted for by many factors.
4.5.1.
The purpose of the classification
A classification for research purposes must be better defined than one used
for field work by relatively unskilled staff.
14
4.5.2
The need for continuity
An outdated classification may continue to be used in a long term programme
so that results are comparable over a long period.
4.5.3
Regional variations in leprosy
A good example of this is the use of "maculo-anaesthetic" to include both
subpolar tuberculoid and subpolar lepromatous patients in areas where
midrange borderline leprosy is uncommon.
4.5.4
The classification of Ridley and Jopling
This is becoming the most generally used classification for patients in hospital,
and particularly for research studies, its use is now mandatory in
programmes involving immunological investigations. The defmitionsof the five
groups are both clinical and histopathological, and there is good agreement
between the two when clincian and pathologist are reasonably experienced.
Polar tuberculoid and polar lepromatous are called TT and LL respectively,
and mid-range borderline is BB. The types of leprosy between them are BT
and BL. The relationship of this classification to others is shown in Table 1.
The most important point to note is that, compared to the 3 group classifica
tion, BB is more narrowly defined than borderline. BT includes some patients
who would be tuberculoid and some borderline: similarly BL includes some
who would be lepromatous and some borderline.
4.6 The importance of classification
There are number of reasons why it is important to be able to classify patients
with leprosy reasonably accurately.
TABLE I
Different Nomenclatures in the classification of leprosy.
TT
BT
Lepromatous
Tuberculoid
Borderline
Polar
Tuberculoid
Intermediate forms
Non Bacilltferous
LL
BL
BB
Polar
Lepromatous
Bacilliferous
15
with atypical lesions. To know the range
of different appearances of skin lesions in leprosy can be important for dia
gnosis, particularly for those who do not frequently see or treat leprosy
patients.
4.6.1 Problem cases can be seen,
period of treatment depends on the type of disease. Patients
with tuberculoid leprosy may be cured in 2 or 3 years, but borderline cases
need longer. Lepromatous leprosy requires at least 10 years treatment: and
because of the risk of reinfectionmany authorities advocate life-long treatment.
4.6.2 The
and their nature varies with the type of
disease, and can be forecast with reasonable accuracy if the patient is ac
curately classified. Most of the complications could be described by the
patient as “the disease is getting worse1'; so accurate warning is important
if patient cooperation is to continue. Few patients will return to a clinic if
they think that treatment has made their disease worse.
4.6.3 The risk of complications
5.
NERVE INVOLVEMENT IN LEPROSY
Nerve involvement is always present in leprosy, can and usuallybe detected
clinically. Bacilli can be found in nerves at any level from the most peripheral
nerve twigs to the dorsal root ganglia. But the maximum concentration of
bacilli, and therefore the greatest damage, are to be found in two “zones'',
the dermal nerves, and certain sites of nerve trunks.
5.1.
Nerve Trunk Involvement
The “site of predilection" for nerve enlargement and damage are shown in
Fig. 2. Most of them are at positions where the nerve lies close to the skin
and passes over a bone structure. The nerve damage leads to sensory, motor
or mixed loss according to the nerve affected. Damaged nerves are usally
enlarged, and sometimes tender to palpation: but at a late stage in the disease
they may be small and fibrotic.
The nerve trunks are damaged at the same sites in all types of leprosy. But
in.tuberculoid leprosy only one or two trunks, usual ly near the skin lesion(s) are
affected. In lepromatous cases, however, the involvement is symmetrical and
affects all the sites of predilection: but damage occurs at a late stage in the
disease, the mere presence of bacilli in the nerves not necessarily seriously
16
impairing their function. Thus in lepromatous cases there can be extensive
skin lesions but little muscle weakness. Patients'with borderline leprosy have
the worst of both worlds; nerve trunks are extensively involved and liable
to be rapidly damaged.
figure 2
“Sites of Predilection” for nerve enlargement in leprosy.
17
5.2
Dermal nerve damage
As with nerve trunks, dermal nerves are damaged most rapidly in tuberculoid
leprosy. Tuberculoid patches are usually anaesthetic and always have some
degree of sensory impairment; but those in lepromatous leprosy often show
almost normal sensation, though there are many bacilli in the nerves.
Anaesthesia is varible in borderline leprosy.
In diffuse lepromatous leprosy, the maximal bacillary concentration is usually
in the cooler areas of the body, so sensory loss may be more marked in the
distal parts of the limbs. In advanced cases the trunk may be, anaesthetic,
but the axillae and groins are.spared.
5.3
Histophathological changes in nerves
The reason for the ability of m.leprae to enter peripheral nerves is unknown.
But, once within the nerve, the bacilli are to some extent protected from the
host immune response. Thus, in tuberculoid and borderline leprosy, bacilli
are often to be found in nerves inconsiderably higher concentration than
elsewhere. Ultimately the nerves are damaged by epithelioid granuloma
formation withinthem.
In lepromatous leprosy there is little or no host resistance to the infection,
and nerves are not sites of high bacillary concentration compared with skin.
They are damaged by bacillation of the perineurium (leading to loss of its
protective function); by the influx of inflammatory cells attracted by intraneural bacilli; by the sheer bulk of bacillary material, in both Schwann cells
and invading macrophages; and by fibrosis occuring in the inflamed nerve.
6.
REACTIONS IN LEPROSY
Reactions may be defined as "the clinical manifestations of alterations in
the immunological balance between host and infecting organism which are
not directly caused by the progress or regression of the disease". There are
two important types of reaction, "reversal" reaction and "Erythema Nodosum
Leprosum", in neither reaction are the "trigger” mechanisms known.
6.1.
Reversal reaction
This occurs in patients with borderline leprosy, and is associated withan
increased cell-mediated immune response to antigens of m. leprae, which can
be demonstrated in vitro by means of the lymphocyte transformation test. It is
probably the most clearcut example of delayed hypersensitivity (Coombs and
Gell Type 4 reaction) causing clinical disease. The name "reversal reaction”
18
was given because it appeard to reverse the drift towards the lepromatous
pole that tends to occur in patients with untreated borderline leprosy.
Clinically this reaction is characterised by increased oedema and erythema
of previously present lesions. If severe, there is fever and general oedema,
and occasionally ulcerationof the skin lesions. Histologically there is oedema,
epithelioid granuloma formation, and influx of lymphocytes. The reaction can
also affect nerves in which m.leprae are present: the oedema and granuloma
formation are liable to give rise to pain and swelling of nerve trunks, with
sudden severe nerve damage. On occasion nerves but not skin can be
affected, probably because the concentration of bacillary antigen in the
nerve is higher.
6.2
Erythema Nodosum Leprosum (ENL)
This condition is very different to the erythema nodosum that occurs in
tuberculosis and other conditions. The name should be considered mainly as
descriptive: red (erythema) lumps (nodosum) in lepromatous leprosy (lepro
sum). It is also an unsatisfactory name, as ENL can affect many other tissues
than skin.
ENL occurs only in lepromatous leprosy, and is associated with the deposition
of immune complexes, particularly in tissues where m.leprae are to be found.
It is thus a disorder of humoral immunity, and may be considered as aclinical
manifestation of the Arthus phenomenon (Coombs and Gel I Type 3 reaction).
The skin lesions consist of erythematous nodules which may be intra-or sub
cutaneous, and are often tender and painful. They disappear after a few days.
The condition may be episodic, with crops of nodules developing every few
weeks or at even longer intervals: or new nodules may appear day by day
for months or years. There may be fever, and the lesions sometimes
ulcerate; indeed, severe ENL is a life-threatening condition.
When ENL lesions have subsided the skin usually returns to normal, though a
residual mottled hyperpigmentation is not uncommon. In severe recurrent ENL,
however, chronic oedema with fibrosis within the skin may develop, causing
stiffness and sometimes bizarre contracture deformities of the hands or feet.
Histologically, ENL lesions consist of dense polymorph foci in the dermis,
sometimes with associated vasculitis. After a few days, before the lesion has
fully resolved, the polymorphs are replaced by loose collection of lymphocytes.
ENL can affect other tissues where m.leprae are to be found, particularly
nerves, which however, are damaged more slowly than in reversal reaction,
so that a nerve can be tender and painful for some weeks but retain almost
normal function. Other tissues which can be affected include lymph nodes,
19
testes, and eyes, all of which can become inflamed. Hepatosplenomegaly is
occasionally seen. More rarely polyarthritis or glomerulonephritis develop.
The extent to which the lesions of different tissues are caused by local
immune complex formation or deposition of circulating complexes is not
known, and it is uncertain what antigens are involved.
7.
7.1
IMMUNOLOGY IN LEPROSY
Cell mediated immunity (CMI)
m.leprae is an obligatory intracellular parasite, and, as is the case with other
such micro-organisms, resistance to the infection is predominantly a function
of CMI. It appears to be well established that there is depression of CMI
responses to antigens of M.leprae, particularly in lepromatous leprosy, where
the defect is complete and probably permanent. In addition, a non-specific
depression of the responses to stimulation with phytohaemagglutinin (PHA)
and other mitogens has been observed in untreated lepromatous leprosy,
but it tends to recover during effective anti-leprosy chemotherapy.
CMI can be assessed in vitro by the lymphocyte transformation test (LTT),
in which circulating lymphocytes are separated, suspended in cell culture
medium, and exposed to the test antigen. Lymphocytes responding by blast
transformation indicate their sensitisation to the antigen.
When whole washed M.leprae are used as antigen, responses are higher at
the tuberculoid end of the spectrum, and usually very low in lepromatous
cases. However, the degree of erythema of the patient's skin lesions affects
the result; the greater the erythema, the higher the responses in all types of
leprosy. The highest responses are found in reversal reactions, where,
however, the rise is transient, and the response falls as the reaction subsides.
It has not been demonstrated that any of these responses are relevant to
resistance to the infection, and the LTT as it can be performed at present is
of no value for diagnostic or classification purposes.
7.2
Humoral immunity
The ability of the host to respond to the presence m.leprae by producing
antibodies to mycobacterial antigens appears to be normal. Such antibodies
are present in large amounts in patients with active lepromatous leprosy, the
amount decreasing towardsthe tuberculoid end of the spectrum. The role of
20
these antibodies in the pathogenesis of leprosy remains unknown. However,
by immune complex formation, they are associated with the damaging compli
cation of ENL.
7.3
Macrophage function
Most tissue macrophages are derived from blood monocytes. In response to
various stimuli, including products of activated lymphocytes, they migrate into
the tissues, where they can adopt a wide variety of forms. In leprosy these
forms include epithelioid cells, histiocytes containing globi, foam cells, and a
variety of multinucleated cells, according to the type of leprosy and the degree
of activity or regression of the disease.
It is clear that in the lesions of lepromatous leprosy macrophages have im
paired ability both to kill M.leprae and also, in patients under treatment, to dis
pose of bacillary lipid degeneration products. There are conflicting reports on
the ability of lepromatous macrophages in vitro to lyse autoclaved m.leprae:
it is therefore uncertain whether the in vivo deficiency is a defect in the
macrophage population per se or due to lack of stimulation by other cells.
7.4
The lepromin test
Standard lepromin is prepared from biopsies of nodules from patients with
lepromatous leprosy. The biopsy material is homogenised, and some of the
skin material removed by centrifugation. The crude preparation, containing
both human skin and bacillary components, is autoclaved and standardised
according to the bacillary count to a concetration of 1.6 x 10’ bacilli per ml.
The preparation is injected intradermally in a dose of 0.1 ml, and the 48-72
hour ("Fernandez'') and 3-4 week ("Mitsuda") readings recorded.
The early reading indicates delayed hypersensitivity to the injected antigens.
In healthy subjects in non-endemic areas it is usually but not invariably
negative. The late reading, on the other hand, is commonly positive even in
non-endemic areas, and may indicate ability of the subject to initiate or
amplify a response to the injected antigen. Persons who are persistently
lepromin negative may therefore be at increased risk of contracting leprosy.
In leprosy patients both reactions are strongly positive in tuberculoid, and
negative in lepromatous cases.
A positive lepromin test (whether early or late) is not an indication of exposure
to M.leprae; nor is it a diagnostic test for leprosy. It can, however, be of help
in the classification of known cases of leprosy. There is, at present, no sero
logical or skin test available for the diagnosis of leprosy.
21
8.
DIAGNOSIS AND
DIFFERENTIAL DIAGNOSIS
Diagnosis of leprosy
8.1
There are three cardinal signs of leprosy:skin lesions. The presence of localised skin lesions (which are usually
hypopigmented and may be erythematous), which show sensory loss, and
which do not coincide with the territory of distribution of particular nerves.
a)
b) The presence of acid -fast bacilli in the skin.
c) Nerve enlargement at the sites of predilection.
Of these signs, the first is diagnostic alone. Acid-fast baci III can occasionally
be found in the skin in other conditions than leprosy; and it must be remem
bered that they are usually not found in tuberculoid leprosy. However, sensory
loss is invariably present in tuberculoid skin lesions, though it may not be
found in lepromatous macules (which, however, contain acid-fast bacilli).
Enlarged peripheral nerves are very occasionally found in other conditions
than leprosy. A more common source of error, however, is failure to recognise
that normal sized nerves can be seen and felt.
Differential diagnosis of leprosy
8.2
Leprosy can mimic a wide variety of skin diseases, but if it is always con
sidered as a possible differential diognosis and the cardinal signs searched
for, mistakes are unlikely to be made.
8.2.2
From neurological diseases
Neural leprosy with no visible skin lesions is uncommon, but the patient who
has been treated for some years can present a problem in diagnosis, as the
skin lesions may be all but invisible, and skin smears can often be negative
for acid-fast bacilli. Such patients may conceal their past history.
Neurological conditions most commonly confused with leprosy include:a) Spinal cord diseases such as syringomyelia, amyotrophic lateral sclerosis,
or motor neurone disease.
b) Peripheral nerve diseases, including ;-
i) those caused by nerve compression, such as spinal root pressure,
carpal tunnel syndrome, and Bell’s palsy.
ii) Polyneuritis of any aetiology.
22
c) Muscle diseases, such as myopathies and myositis.
d) Disease with "trophic" manifestations, such aS diabetes mellitus, tabes
dorsalis, and congenital indifference to pain.
Important points to remember are that:-
a) Leprosy never causes upper motor neurone lesions, and proximal muscles
are very rarely involved.
b)
Sensory loss in leprosy may be maximal peripherally, but there are
usually islands of preserved sensation on the hands or feet, and the
tendon reflexes are preserved and often brisker than usual. Moreover
position sense is almost always preserved.
c)
Leprosy never damages the brain or spinal cord.
8 2.3 From limb deformities
Many limb deformities, including congenital defects, those due to poliomyelitis,
contractures such as Dupuytren's, old injuries, or yaws may, if taken in
isolation, be mistaken for leprosy. The diagnosis of leprosy can, however,
almost always be excluded by careful inspection of the whole body.
9.
9.1
CHEMOTHERAPY OF LEPROSY
Drugs active against leprosy
Sulphones
These include dapsone (4'4 diamino diphenyl sulphone, DDS) and diacetyl
sulphone (DADDS). Other sulphones, such as glucosulphone (Promin), sulphoxone sodium (Diasone) and solapsone (Sulphetrone) are now obsolete.
I_ong-acting Sulphonamides
These have the same mode of action as the sulphones, and many disad
vantages compared with them.
Thiureas
Thiacetazone (Amithiazone, TBI) is the only preparation now being manu
factured, though thiambutosine (CIBA 1906, DPT) may be available from
stocks for a year or two.
23
Rifampicin
(The only fully bactericidal drug against leprosy).
Notes on these drugs and their uses are given at the end of this section.
9.2
Principles of chemotherapy in leprosy
Whatever drug is used, these are three phases in treatment; they can be
most clearly defined in lepromatous leprosy.
Phase 1 — During this period most of the bacilli are killed. With most drugs
this stage requires about 6-12 months; but it is much less when rifampicin
is used. It is completed when most of the bacilli in skin smears have
become fragmented.
Phase 2 — During this period the drugs kill most of the surviving bacilli,
and the body mechanisms dispose of the killed ones. This phase is com
pleted in about 5 years, when bacilli are usually not found in skin smears.
Phase 3—At the end of Phase 2 there are still “persisting” bacilli which
are drug sensitive but in some way dormant. They appear to survive therapy,
and are liable to cause relapse if treatment is discontinued too early. If the
disease is to be cured, treatment must continue till these "persisters" have
died, whether from drug activity, host resistance, or "old age”: this period
is probably 5-10 years, but may be longer.
In non-lepromatous leprosy the principles are the same, but the greater the
degree of host resistance, the shorter the period required for treatment, as
shown in Table 2.
TABLE 2
Different “Phases” in the Chemotherapy of Leprosy
24
Period of Treatment in Years
Type
of Leprosy
Phase 1
Phase 2
Phase 3
Total
Indeterminate
0
1
1
2
Tuberculoid
0
1
1
2
Borderline
1
2
3
6
Lepromatous
1
5
10
16
This table requires comments:-
1.
The figures assume that the bacilli are fully sensitive, and that treatment
is taken regularly and daily in full dosage. Most patients are not fully
regular, so these periods are the minimum that should be considered.
2.
In borderline cases, longer treatment is needed if they are closer to the
lepromatous pole: a shorter period could be risked if they are close to
tuberculoid.
3.
The question of whether patients with lepromatous leprosy should take
lifelong treatment to prevent re-infection is as yet unsettled. In the absence
of factual knowledge, the patient’s wishes should be the deciding factor.
9.3
Single or multiple therapy
There are two reasons for using multiple drug regimes in other diseases
particularly tuberculosis:
1.
To cure the disease more quickly. In tuberculosis only regimes including
2 or more bactericidal drugs will shorten the period of treatment. In leprosy
only one fully bactericidal drug, rifampicin is available; and, there is as
yet no evidence that including it in combined treatment regimes cures
the disease more quickly. Moreover, there is no drug which is known to have
a specific activity against "persisters" in leprosy, and which can therefore
shorten the final phase of treatment.
2.
To prevent drug resistance. There is now ample evidence that resistance to
dapsone is becoming common, and therefore that all patients with lepro
matous leprosy should receive dual therapy for at least the first year of
treatment, both drugs being used in maximum dosage throughout. In nonlepromatous leprosy the bacillary load of the patient is small, and the risk
of acquired drug resistance therefore less. At present, monotherapy with
dapsone in full dosage is advised, but this recommendation may need
revision if substantial numbers of patients are found to have developed
primary drug-resistant infections.
A further indication for multiple drug therapy is as a period of supplementary
treatment for patients with lepromatous leprosy whose treatment was initiated
with dapsone in low dosage, and who are therefore at special risk of
developing dapsone resistance. The best drug combinations, and the duration
of treatment required to kill the population of resistant mutants before they
have multiplied sufficiently to give clinical evidence of dapsone resistance,
are not yet known.
9.4
Dapsone resistance in leprosy
Resistance to dapsone occurs in patients with lepromatous leprosy, and is
acquired during the course of monotherapy, usually with submaximal dosage
of sulphones. The history is characteristic — intial improvement, followed by
relapse despite continued treatment with dapsone.
As dapsone is well absorbed orally, the only two possibilities in such cases
are dapsone resistance, or that the patient is not taking his treatment. Most
patients tell the truth on sympathetic questioning. However, the manage
ment should include a period of treatment with dapsone in maximal dosage,
as fully supervised as possible, and with regular assessments, which must
include as a minimum body drawings and skin smears. If possible, dapsone
excretion in the urine should be checked. If it is certain both that the treat
ment is being taken, and that the clinical state is deteriorating, then the
diagnosis of dapsone resistance is proved. Independent evidence can be
provided by mouse foot pad tests, but they are no more reliable than a well
performed clinical trial, and may take as long.
Such a trial is essential to the management of patients suspected of dapsone
resistance. In addition to proving the diagnosis, it convinces the patient that
dapsone no longer helps his disease. This will make it easier to persist with
prolonged treatment with other drugs, which usually have more side effects,
and are always more expensive, than dapsone.
9.5
9.5.1
Notes on anti-leprosy drugs
Sulphones
Dapsone(DDS)
Still the drug of choice for treatment because:
1. It has a very high therapeutic ratio.
2. Side effects in normal dosage are uncommon.
3. It is slowly excreted, therefore once daily dosage is possible.
4. It is inexpensive.
5. It is stable, and tablets keep indefinitely.
6. It can be given by injection if necessary.
Dosage:
Use 50-100 mg daily at all times in all adults (for children 1-2 mg/kg body
weight).
26
DO NOT use a "slow build up" at the start of treatment; it does not lessen
reactions and does make dapsone resistance more likely.
DO NOT reduce the dosage or stop treatment during reactions — it does not
lessen the reaction significantly and will delay the cure of the patient.
Side effects:
Drug allergy (skin rash, fever, jaundice) — always develops within 2 months
of starting treatment.
Fixed drug eruption.
Difficulty in sleeping.
Anaemia.
Indications:
For all patients with leprosy except those with:
1. Sulphone or sulphonamide allergy.
2. Dapsone resistance.
A note on "Dapsone Intolerance":
This unsatisfactory phrase is used to cover two conditions:
1. Side effects. Occasional patients develop abdominal discomfort or sleep
lessness even on average doses of dapsone. These symptoms can nor
mally be controlled by giving the dapsone in divided dosage with meals,
or (in the case of difficulty in sleeping) as a morning dose.
2. The development of reactions in patients receiving dapsone. Reactions are
not directly related to dapsone therapy and are not an indication for
altering the treatment.
Di-acetyl Sulphone (DADDS)
Advantage:
Is given as a very long lasting injection:
Once in 2 months=2.5mg dapsone daily;
once in 1 month = 5. mg dapsone daily.
Disadvantages:
Gives blood dapsone levels that are too low to be satisfactory, and may pro
long the period of treatment required to cure the patient.
Indication:
The treatment of non-lepromatous leprosy, if fully supervised treatment ad
ministered every 1—2 months is desired.
27
TT leprosy; a single hypopigmented lesion,
with two tiny "satellite" lesions.
BT leprosy. The lesions have raised edges,
and the lowest one shows central healing.
BT leprosy. Multiple hypopigmented macules,
some showing a little central healing.
"BB leprosy. Raised lesions of varying sizes,
including a large plague with a ‘punched out’
clear centre"
‘“BL Leprosy. Mildly asymmetrical lesions of
fface, trunk and arms"
“Diffuse lepromatous leprosy, showing com
plete symmetry, loss of eyebrows and mild
'leonine face1 "
“Nodular lepromatous leprosy. The nodules of
the face could be described as 'histoid' ”
Enlargement of the Auricular nerve.
Photographs : Dr. J.A. Kinnear Brown
Contra-indications:
1. It must be used only as part of combined therapy in the treatment of lepromatous leprosy.
2. It should be administered only when it is certain that patients do not have
DDS allergy.
9.5.2
Long-acting Sulphonamides
These act in the same way as DDS, but have a much lower therapeutic
ratio, mote frequent side effects, and are more expensive.
9.5.3
Thiureas
Thiacetazone (TB1, Amithiazone)
Advantages:
Once daily dosage; cheap.
Disadvantages:
Many side effects except in Africans (skin rashes, fever, jaundice).
When used as monotherapy lepromatous patients develop resistance within
2-3 years.
Indications:
1. As monotherapy in patients with non-lepromatous leprosy who have
dapsone allergy.
2. As part of combined therapy in lepromatous leprosy.
Thiambutosine (Ciba 1906, DPT)
Advantages:
Very few side effects (occasional stomach pain)
Disadvantages:
Must be taken 2 (or preferably 3) times daily.
Expensive.
When used as monotherapy, lepromatous patients develop resistance within
2-3 years.
9.5.4
Ethionamide
Mode of action probably the same as the Thiurea drugs.
Advantages:
High therapeutic ratio.
Disadvantages:
Toxic (nausea, malaise).
Rather expensive.
Indications:
For research studies only.
9.5.5
Streptomycin
Different mode of action from other anti-leprosy drugs.
Disadvantages:
Need at least twice weekly injection.
Toxic (vertigo due to 8th cranial nerve damage).
When used as monotherapy, resistance develops in 2-3 years in lepromatous
cares.
Not cheap.
Indications:
1. In combination with dapsone in treating lepromatous leprosy with severe
ulcerating primary nodules. (Its benefit may be due to its activity against
secondary infection).
2. In combination with other drugs in the treatment of dapsone resistant
leprosy.
9.5.6
Clofazimine (Lamprene, B.663)
Mode of action different from sulphones, thiurea compounds and streptomycin.
Advantages:
In lepromatous cases - ENL less frequent and severe.
Resistance uncommon (none yet reported).
In non-lepromatous cases - Probably none.
Disadvantages:
Skin discolouration.
Abdominal pain common on high dosage.
Expensive.
Capsules are damaged if stored at high temperatures.
Indications:
Patients with lepromatous leprosy and severe reccurent ENL or neuritis (in
combination with dapsone); high dosage (100 mg daily or more) is usually
required.
31
0537’
Patients with sulphone resistance (in combination with another non-sulphone
drug); minimum dosage should be 100 mg on 3 days per week.
9.5.7
Rifampicin
May be similar to clofazimine in mode of action (cross-resistance has been
demonstrated in cultivable mycobacteria).
Advantages:
Kills m.leprae more rapidly than other drugs.
Disadvantages:
Serious toxicity, particularly in intermittent use at high dosage (over 900mg).
Very expensive.
Indications:
1. When it is important to render a patient with lepromatous leprosy noninfectious as rapidly as possible.
2. In research studies.
10. THERAPY OF REACTIONS AND NEURITIS
Both reversal reactions and ENL can occur in patients who are not receiving
anti-leprosy treatment; but both (and more especially ENL) are more com
monly seen in treated patients. When patients under treatment develop nerve
damage, it is due to a reaction occurring within the nerve. Such nerve damage
is usually associated with paraesthesiae (in the case of dermal nerves) or
tenderness of nerve trunks at the sites of predilection. Thus reactions and
neuritis represent the same process occurring in skin and nerves respectively
They may occur singly or together; but the principles of management are
identical.
10. 1 Treatment of Reversal Reaction
The most important decision is whether the reaction is mild or severe: the
definitions are summarised in Table 3. It is only necessary to add that pro
longed (i.e. 6 weeks or more) mild reversal reaction should usually, for treat
ment purposes, be managed as "severe" reaction, as it tends to cause gradual
nerve damage.
32
TABLE 3
Definitions of mild and severe Reversal Reaction
Site
Mild Reaction
Severe Reaction
Skin
Erythema + mild oedema
of previously visible
skin lesions.
Marked erythema and
oedema of previously
visible skin lesions
OR
Ulceration of lesions
OR
The appearance of new
small lesions
OR
Oedema of the hands and/
or feet.
Dermal
Nerves
Paraesthesiae without
increasing anaesthesia.
Increasing anaesthesia
of skin lesions OR of
hands and/or feet.
Nerve
trunks
Even minimal nerve
trunk tenderness
without loss of
function is a danger
sign of severe neuritis
and needs assessment
for loss of function,
which can occur very
rapidly.
Evidence of loss of
loss of function +
nerve pain and/or
tenderness
Systemic
illness
Mild discomfort and
slight fever.
Marked fever, malaise
and discomfort.
Whether the reaction is mild or severe, anti-leprosy treatment must be contin
ued, and there is no proved benefit from changing the treatment, either by
altering the dosage of dapsone or by changing to any other anti-leprosy drug
33
10.1.1
Treatment of Mild Reversal Reaction
Give mild analgesics as required.
(a)
If available, give fouadin (stibophen) injections.
(b)
A course is either 2-3 ml daily for 4-7 days
or 5 ml every 2-3 days for 3 or 4 injections
(c)
For out-patients, warn them to return at once if the reaction becomes
more severe, or persists despite treatment.
10.1.2
Treatment of Severe Reversal Reaction
Only corticosteroid drugs are of any value. For most patients Prednisolone
30 mg daily is enough; occasionally if there is no improvement in a few days,
double or treble dosage should be given for a week or two till symptoms are
controlled. Most patientswill need 20-30 mg daily for about 3 months and
then gradual reduction of dosage. BT cases seldom need steroids for more
than 6-8 months, but in BL patients, the reaction often persists for a year or
more; the dosage and duration of treatment must therefore be adjusted for
individual cases, the most important factor being the prevention of permanent
nerve damage.
10.2
Treatment of ENL
The treatment of ENL is less straightforward than that of reversal reaction,
for two important reasons:a)
The course of ENL is more variable, ranging from a single crop of lesions,
through episodic ENL persisting for some months, to, in very severe cases,
a systemic illness with constantly present lesions for up to 5 years or so.
b)
More drugs are available for effective treatment. In particular the need for
steroids has been lessened since the advent of clofazimine and thalido
mide.
10.2.1
Clinical patterns of ENL
In general, ENL can be considered as either episodic or continuous. In Africa
most patients develop episodic ENL, but in paler skinned races there is a ten
dency for ENL to be more continuous, prolonged, and severe.
As is the case in reversal reaction, it is important to decide whether the ENL
is severe or mild. This decision, however, is easier to make. Severe ENL is
present if any of the following criteria are met:-
34
) Skin lesions that ulcerate.
a,
bo) Serious nerve pain or evidence of nerve damage.
c)
Involvement of the eyes or testes.
d)
High fever and systemic illness.
‘10.2.2 The treatment of episodic ENL
I Mi Id attacks of ENL require the same management as mild reversal reaction,
that is:-
a)
Analgesics as required.
b)
A course of fouadin injections, if available.
c)
Warning to outpatients to return to the clinic if the reaction persists or
recurs.
In addition
d) Chloroquine 250 mg 3 times daily for 2 weeks is sometimes helpful.
An attack of mild ENL is self limiting, seldom persisting for longer than 2
weeks. Repeated attacks respond to repeated treatment, though courses of
fouadin should normally not be given more often than monthly.
A severe attack of self limiting ENL seldom persists for longer than 2-3
weeks, so the initial treatment should be with a course of a steroid (usually
prednisolone) for about the same period. Most patients respond well if given
Prednisolone 30 mg daily for 1 week.
then 15 mg daily for 1-2 weeks.
The dosage should then be stopped; it should not be gradually tapered off.
Repeated attacks of severe ENL need repeated courses of steroid treatment.
However, if patients develop 3 or 4 such attacks in a period of 2 months or
so, experience indicates that the ENL is likely to persist for many months.
Such patients should be treated with clofazimine. The initial dose is 100 mg
3 times daily, for about a month: at the end of this time severe attacks of ENL
will usually have been suppressed into mild attacks. Clofazimine takes 2-3
weeks to develop its full action; after about a month the dose can usually be
reduced to 100 mg daily or twice daily, which should be continued for a year
or so, or longer if ENL still persists. Episodes of ENL during clofazimine therapy
should be treated with fouadin or steroids according to their severity,
35
If thalidomide is available it is the drug of choice for treatment of ENL except
in women of child bearing-years, for whom it should never be prescribed. It
acts rapidly, and should be used in the same way as steroids. 100-300 mg
daily is usually effective; because of its sedative action it is best given at
night. Polyneuritis has never been observed as a complication in leprosy
patients:! ndeed nerve function often shows rapid and permanent improvement.
If supplies of thalidomide are restricted, the drug is best reserved for patients
who, despite clofazimine, need repeated courses of steroids. In this way the
steroid dosage can be reduced and the dangers of steroid toxicity much
lessened.
10.2.3 The treatment of continuous ENL
The principles are the same as in the management of episodic ENL, but
because treatment must be continuous and uninterrupted, the risks of steroid
toxicity are much greater, and the need to employ the steroid-sparing drugs,
clofazimine and thalidomide, correspondingly greater. Treatment should not
be in such high dosage that the ENL is fully suppressed; patients should
show occasional attacks of ENL, though not so severe as to damage nerves,
eyes, or testes.
10.2.4 Anti-leprosy treatment and ENL
It is essential to continue anti-leprosy treatment in full dosage during ENL,
and it has been shown that dapsone in full dosage has very little effect on the
severity of ENL. If anti-leprosy treatment is discontinued for periods of months,
a mixture of ENL and active leprosy known as "progressive lepra reaction",
which can be fatal, is liable to develop. In theory, dapsone can be discontinued
if patients are receiving clofazimine; but in practice, if this is done, patients
attribute the reaction to dapsone, and are unwilling thereafter to take it regu
larly. Clofazimine is therefore best prescribed as additional therapy to
dapsone, and it may have the incidental benefit of lessening the risk of
subsequent dapsone resitance.
36
11.
11.1
THE EYE IN LEPROSY
Non-lepromatous leprosy
In non-lepromatous leprosy only the "outside" of the eye is affected by
anaesthesia, 7th cranial nerve weakness, or both.
11.1.1 Lagophthalmos can cause exposure of the cornea. Possible sequelae
include conjunctivitis, exposure keratitis, and corneal ulceration - the results
of failure of eyelid function, which is to clean the cornea and maintain its
moisture.
blink reflex, and
is therefore liable to cause keratitis and ulceration. When combined with
lagophthalmos the eye is in serious danger, as inflammation can reach the
point of perforating corneal ulceration without the patient being aware of
anything grossly amiss.
11.1.2 Corneal anaesthesia blocks the afferent arm of the
11.2
Lepromatous leprosy
In lepromatous leprosy nodules or plaques can .form on the eyeball itself,
particularly in the upper outer quadrant and at the corneoscleral junction. The
treatment is as for the systemic disease; it should be remembered, however
that lepromas of the eye are most commonly seen in drug-resistant cases.
Lagophthalmos and anaesthesia are less common than in non-lepromatous
leprosy. However, m .leprae are present in the iris and ciliary body, and can
cause iridocyclitis which can lead to blindness by several mechanisms:a)
Inflammatory cells and exudate form in the anterior chamber, and in the
space behind the cornea (where they can deposit as keratitic precipitates):
they obstruct the canals of Schlemm and can cause glaucoma, with resul
tant optitrophy and blindness.
b)
Another cause of glaucoma is adhesion of the inflamed iris to the lens.
These synechiae, if extensive, can obstruct the flow of aqueous fluid from
the posterior chamber to the anterior chamber. The increased pressure in
the posterior chamber then pushes the iris forward causing mechanical
obstruction of the canals of Schlemm. Both these processes cause glau
coma.
c)
Synechiae can distort the shape of the pupil, pull it off centre, and so inter
fere with vision. They can also lead to cataract formation and blindness.
37
d)
Prolonged inflammation of the ciliary body can impair its function of
aqueous production, and so the eye becomessoft, collapses, and "dies".
("Phthisical Eyeball").
Sclertitis may be associated with iridocyclitis. It takes the form of a red
triangular zone in the inter-palpegral area of the sclera, which is tender to
touch. Treatment is as for iridocylitis.
11. 3 Management of the eye in leprosy.
11.3.1
Permanent lagopathathalmos
If mild (4 mm or less), eye shutting exercises can sometimes reduce it. But
this degree of lagophthaloms often causes very little harm. This is because
whenever the eye is shut, including during sleep, the eyeball rolls upwards
and outwards ("Bell's phenomenon") so placing the cornea under the upper
eyelid.
If there is more than 5 mm of lagophthalmos, a tarsorrhaphy is usually
required. Mechanical aids, such as artifical tears and eyeshades to protect
the exposed eye at night, can also help to reduce the risk of inflammation of
the eye. If anaesthesia is not present, various surgical procedures (such as
temporalis muscle transfer) to restore the blink, will help. But if there is
impaired sensation, and therefore the stimulus for blinking is not present, the
patient seldom makes good use of the operation
two varieties: an acute type, lasting afew
days, often associated with ENL;and a chronic variety which may continue
for many months. The principles of management are the same, and can be
expressed alphabetically:
11.3.2. iridocyclitis. There are
A. Atropine — this dilates the pupil, prevents synechiae, and reduces the risk
of glaucoma.
b.
Blindness is the likely result of untreated uveitis.
c. Corticosteroids, given locally as eyedrops or ointment, systemically, or
most effectively of all by subconjunctival injection.
D. Diamox (acetazeolamide) if there is raised intra-ocular pressure
11.3.3 Other eye complications
Both lagophthalmos and trachoma (which is often common in areas where
38
leprosy is found) can cause distortion of the eyelids with consequent
ectropion or entropion. Correction of these deformities by minor surgery
will often be valuable, particularly if keratitis is being caused by eyelashes
rubbing on the cornea.
12.
12.1
PHSYICAL THERAPY IN LEPROSY
Exercises
In leprosy a motor nerve is often only partially destroyed, leaving the muscles
it supplies weak but still functioning. Active exercises in such cases encourage
hypertrophy of the remaining muscle fibres and recovery of strength. Even
if a muscle is completely paralysed, passive exercises which put the joints
through their full range of movement several times a day will prevent
contractures. Simple exercises, particularly for the hands, take only a minute
or two a day—patients should be taught how to do them at home.
12.2
Skin Care
Skin that is anaesthetic has also usually lost the sweat and sebaceous glands.
It tends to be dry, and to crack and become infected more readily than
normal skin. Most of these problems can be prevented. The skin, particularly
of the hands and feet, is too dry; this can be remedied by soaking them in
water for 15-30 minutes and the absorbed moisture retained by applying
any ointment or oil and rubbing it into the skin.
13.
13.1
THE FOOT
IN LEPROSY
The Aetiology of "Trophic Ulcers"
The foot in leprosy can be damaged and deformed as the end result of
anaesthesia, paralysis of the intrinsic or extrinsic muscles, or bone damage.
13.1.1 Paralysis of the instrinsic muscle leads to the development Of claw
toes and undue prominence of the metatarsal heads. Peroneal nerve damage
causes “foot drop", and so abnormal stress on the lateral part of the fore
foot when walking.
39
Bone damage can be due either to osteomyelitis secondary to a
penetrating ulcer, or to a little understood process of softening and
absorption of the bones of the tarsus, and sometimes also of the phalanges.
13.1.2.
the patient can continue to walk on
it long after pain would have stopped a normal person and enforced rest.
Thus trauma leads on to inflammation and ulcer formation. The ulcers tend
to develop in the positions of maximal trauma,- which vary according to the
deformity that is present.
13.1.3 When the foot is anaesthetic,
13.2
Management of the Ulcerated Foot
Almost all ulcers will heal given time and rest without weight-bearing. The
larger the ulcer, the greater the tissue distortion on healing; also when large
ulcers heal there is little subcutaneous tissue, and the skin, adhering to bone,
is more liable to recurrent ulceration. The principles of treatment are the
normal principles of surgical treatment of injuries: debridement, including
removal of dead bone; rest; and antibiotics for acute infection.
Ulcers will sometimes heal even when walked on, provided the body weight
is well distributed by a plaster of paris (POP) cast or by suitable shoes. The
application of a POP cast should be delayed till the ulcer is clean and infection
controlled. In general dressings should be avoided unless they can be rene
wed twice daily: a wet, pus-soaked dressing slows healing —it is better for
the feet, socks, and shoes to be washed carefully with plain water each day.
13.3
Principles of Prescribing Footwear in Leprosy
Use a mioroceiiular rubber insole to distribute the weight uniformly. Extra
padding to form an arch support will relieve pressure on the metatarsal
heads if claw toes are present.
Use sandals if the foot is distorted so that there is a risk of ulcers on the
dorsum or side of the foot. The thongs can be placed to avoid bony
prominences.
Use moulded shoes designed to give maximal support around the edges as
well as on the sole if the foot is reduced in size. "Plastazote” shoes are
the most suitable.
If necessary use a less suitable shoe that the patient will wear rather
than the "best" which, because of its odd appearance, will only be worn
when the patient attends his clinic.
40
14.
THE PLACE OF
SURGERY IN LEPROSY
This section makes no attempt to give any details of surgical procedures or
their indications. It is merely a list of conditions in which surgical treatment
can assist in therapy or rehabilitation. It should be remembered that some of
the common and simple procedures (particularly in the management of in
fection and eye problems) can be undertaken by non specialist doctors or
trained paramedical workers.
14.1
Surgery of infection
Drain abscesses, debride ulcers, remove dead bone from infected lesions.
14.2
Surgery of bone
Arthrodesisof claw toesand of tarsal bones in "disorganised feet"; arthrodesis
of the wrist when there is complete paralysis (flail wrist).
14.3
Tendon transfer operations
For "drop foot" and mobile claw hand.
14.4
Eye Surgery
Tarsorrhaphy, temporalis transfer, ectropion and entropion operations, iridec
tomy for certain cases of glaucoma.
14.5
Surgery of nerves
Release of osteoligamental tunnels where nerves are liable to constriction
(Ulnar, median, tibial). Incision of the nerve sheath. Nerve grafts (experi
mental).
14.6
Plastic surgery
Release of contractures, rebuilding the collapsed nose, injection of inert
plastic to conceal muscle wasting of the hands, eyebrow grafts.
14.7
Amputation for intractable ulceration
41
15.
PRINCIPLES OF
LEPROSY CONTROL
The aim of control of any communicable disease is to reduce its incidence
until it no longer remains a public health problem. The principles that can be
applied, however, vary greatly with different diseases. In smallpox, for
example, the existence of a safe, effective, and long lasting vaccine has made
eradication possible, the principle used being whole population vaccination.
In malaria, the principle of control is interruption of the chain of infection by
mosquito destruction, chemoprophylaxis, and house screens or mosquito
nets. In cholera, control measureschiefly consist of preventing cholera vibros
contaminating the water, their destruction by water purification, and
preventing people ingesting contaminated water.
In leprosy, however, none of these measures is feasible. There is no suffic
iently effective vaccine; there are no intermediate hosts, nor does M.iepare
survive for long outside the body; and chemoprophylaxis is impracticable in
most situations. There is at the present time no possibility of primary preven
tion (i.e., the detection and protection of persons at risk). Leprosy control
must be based on secondary prevention; that is, the early detection and
regular treatment for a sufficiently long period of all cases existing in an
area.
15.1
Early detection (case finding)
This is important in limiting the period of infectivity of the patient, and is
probably the easiest part of leprosy control. The simplest methods are
examination of known contacts of leprosy patients, and limited surveys (such
as schools, factories, army units). In areas where the leprosy prevalence is
low, it maybe necessary to rely on these methods of case finding. Other
patients may be persuaded towards self presentation by suitable publicity:
but the most effective encouragement is a reputation for excellence of the
leprosy treatment programme.
Mass (whole population) surveys are the only way to ensure that all cases
are known, and so are important in evaluating the initial problem(and ongoing
results) of a control programme. But they are unpopular with both staff and
“the mass", hard to supervise adequately, and in some areas operationally
impossible.
42
15.2
Regular treatment for sufficiently long (case holding)
This is the greatest problem of leprosy control, and the quality of a treatment
programme is best judged by its success in this sphere of operation. The
duration of treatment which is required necessitates a quite unusual relation
ship between health worker and patient, so that the patient will attend regu
larly for treatment, and have confidence in the worker's concern for his
welfare. There are so many personality variables that one can wonder why
so many patients do actually attend for treatment for periods of many years,
often showing remarkable determination to do so.
Integration of leprosy treatment with other treatment services is almost
universally accepted as the ideal. Such integration is likely to be of maximal
value in areas where the social stigma of leprosy is greatest. If, for instance
leprosy is treated in a skin clinic, the patient can obtain treatment without
declaring himself a "leper”; this is not possible in clinics where only leprosy
is treated.
15.3
The requirements of a successful control programme
Probably a leprosy control programme in which all infectious patients receive
treatment for 75% of the time will, if maintained for 20yearsorso, "control"
leprosy in that area. The sequential aimsofa programme can be summarised
as follows:-
1.
Early detection and regular treatment of large majority of cases.
2.
Clinical and bacteriological inactivity of all treated cases.
3.
Reduction to negligible figures of new cases.
Such a programme will include in its requirements:1.
Familiarity with the extent of the problem in the area, with related socio
economic factors, and with general attitudes to leprosy.
2.
Evaluation of the reasons for success or failure of already existing pro
grammes, and an outline of priorities and targets for the future.
3.
Assessment of resources, including
Manpower (capabilities, training, responsibilities.)
T ransport and communications
Facilities for referral on specialist advice
Drugs
Money
Other (Publicity and education material, etc.)
43
4.
Development of relationships with concerned bodies, whether Ministry of
Health, area clinics, or village councils.
5.
Concern for individual problems including staff working conditions; and
provision for treatment of patients with special medical and/or social
problems, including continued care of the severely disabled.
6.
Continuous supervision of field programmes.
7.
Ongoing evaluation of programmes, and application in the field of results
of research programmes.
16.
PRINCIPLES OF REHABILITATION
Just as medicine may be defined as “the diagnosis, treatment, and prevention
of disease," rehabilitation may be defined as “the diagnosis, treatment, and
prevention of dehabilitation”. In the context of leprosy, dehabilitation chiefly
affects three areas of life the disease can cause a patient to lose his family
and place in society; his work and means of livelihood; or his self respect.
16.1
Preventive rehabilitation
Regardless of his infectivity, the deformed patient is at greater risk of de
habilitation. Prevention of deformity, by early diagnosis (before deformity
has developed), by the correct treatment of neuritis (which is the chief
cause of deformity developing during treatment) and by health education
(to prevent increase in deformity from contractures, injuries, and infections)
is the most important part of this process that can presently be carried out :
it has been termed "preventive rehabilitation". The surgical correction of
deformity can be a part of this process.
16.2
Active rehabilitation
Active rehabilitation is concerned with providing work for patients, and as
sumes (possibly correctly) that a patient who has a job can also keep his
family and preserve his self respect. It includes two main activities:16.2.1 Workshops for the unskilled
These can provide a limited number of permanent jobs, and should be judged
in business — economic — terms; i.e, will the workshop make a profit
(or at least avoid a loss)! Such workshops can seldom supply more than a
fraction of the need, and must be supervised to ensure that work is adjusted
44
in such a way that it does not cause further damage to patients hands or
feet. Decisions on fair salaries for handicapped persons are often hard to
reach.
16.2.2
Training programmes
The aim of these is to produce workers with skills that enable them to earn
an independent living. They always, by their nature, lose money; but have a
turnover of trainees. Ideally no one should enter such a scheme unless a
"way out” to a paid job is previously, arranged. It is demoralising to be trained
and still have no work at the end.
16.3
Loss of self respect
The diagnosis of the patient with loss of self respect is difficult. One indi
cation is the state of the hands and feet. The patient with recurrent ulcers
and progressive deformity, which defy treatment andhealth education, is prob
ably in this category; he no longer cares about his body (remember, though,
that he may need some deformity to earn satisfactory living as a beggar).
Treatment is almost impossible. Prevention lies chiefly in the attitudes of
friends and relatives, though leprosy clinics which are interested in patients,
and treat them as persons rather than "lepers” will help. In the long run
education away from fear of the disease is the only prevention or cure of
dehabilitation.
17.
PRINCIPLES OF HEALTH EDUCATION IN LEPROSY
Health education may be defined as "the process which leads to better under
standing of health problems and realistic action to solve them.”
It follows that health education is not merely instruction-one way communi
cation. There is little evidence that knowledge—of say the cause of plantar
ulcers—leads inevitably to action to prevent them.
Health education is two-way communication. The focus is clarification, for
both leprosy worker and patient, of what are the real problems, and what,
in a particular situation, is the best action that can be taken to solve them.
The starting point must be the time of diagnosis, and it is hard to overesti
mate the value of a few minutes of discussion, between patient and doctor
(or health worker) at this time. The patient should be given a realistic view
of what dapsone can do, and know in particular that it alone will not reverse
45
deformity, prevent or cure ulceration, or cure anaesthesia. He should also
know roughly how long he will need to take dapsone, and (in many cultures)
be informed that tablets are better than injectionsfor curing leprosy. Because
of the rushed conditions in most clinics, the communication at this initial
interview is likely to more one-way than is ideal; but it may have the effect
of guiding the patient subsequently towards asking the important questions.
Health education often involves work with groups, and a leader who can
listen, summarise, and direct the discussion towards possible action is essen
tial. Health education in a leprosy programme must be evaluated on the
results of the actions it starts, not on the efforts (talks, meetings, films, etc.)
that go into it. A health education programme must therefore include:-
1.
Setting of measurable targets
2.
Training of personnel at all levels by appropriate methods in communi
cation skills (the example of one person is worth 20 lectures!) and en
suring that the information communicated is accurate.
3.
Regular evaluation of the results of the programme.
It should be remembered that patients should not be the sole target of health
education. There are many misconceptions about leprosy among the general
public (and also in medical circles) that health education might aim to cor
rect. In this context key groups of individuals, such as medical and nursing
training schools, teacher training colleges, community leaders, rotarian
groups, and the like, might be selected as specific "targets". Results of
such programmes, however, can seldom be quantified.
46
APPENDIX
1
Technique of "Slit Skin" smears
Skin smears are normally taken from at least one ear lobe and at least 2 skin
lesions; they are best taken from their active edges.
A fold of skin is held between thumb and forefinger tightly enough to prevent
bleeding. An incision about 5 mm long is made in the skin; it should be deep
enough (about 2 mm) to extend well into the dermis. Any blood is wiped
away.
The scalpel blade is then turned so that it is at right angles to the skin slit.
Holding the skin fold tightly, the scalpel blade is scraped firmly down the
incision, thus removing some of the subcutaneous tissue on the tip of the
scalpel. This material is spread as a small thick film on a microscope slide.
When the material has dried, it is fixed by flaming the under surface of the
slide, which should be made slightly too hot to be placed on the bare hand.
Staining is according to the normal Ziell Nielsen technique, except that
m.leprae are decolourised more readily than M.tubercuiosis; decolourisation
must therefore be much briefer, and preferably use less powerful agents,
such as 0.5% hydrochloric acid in 70% alcohol.
The Bacterial Index (Bl)
Over 1000 bacilli in an average oil immersion field
100- 1000 ”
10- 100 ”
1w 110 110 ■■
no "
"
"
••
"
-■
"
10
100
100
........................
"
»
....
..
.........................
"
"
..
"
"
"
= 6 +
=
=
=
=
=
5 +
4 +
3 +
2 +
1 +
Negative
The Morphological Index (Ml)
This is the percentage of bacilli counted which show a uniform solid stained
appearance.
47
APPENDIX 2
Indications and techniques of biopsies
A. Biopsies for Histopathology
1. Indications for skin biopsy
is uncertain. In such cases the biopsy should be
taken across the edge of the lesion, so as to include normal looking
skin.
a) When the diagnosis
Remember, however, that when the lesion is a hypopigmented macule,
the appearance in leprosy is commonly that of non-specific inflammation.
Careful testing for impairment of sensation or deficient sweating will
give a positive diagnosis of leprosy more often than will a biopsy.
b) For accurate classification. When the diagnosis of leprosy is certain the
whole biopsy should be taken from a typical active lesion. Usually it is
best taken fairly close to the edge, and from an erythematous area if
there is one present.
a reaction. In the case of suspected ENL the best lesion
to biopsy is an early one; the histopathological changes may become non
specific in a day or two. If reversal reaction is suspected, the more 'mature'
the lesion the better; often, however, the reaction can only be definitely
confirmed histologically by serial biopsies at intervals of about 2 months.
c) To diagnose
progress of treatment. Such biopsies should be taken
either from the most active looking lesion (particularly if relapse or drug
resistance is suspected) or from an adjacent site to a previous biopsy
(particularly if assessment of a drug treatment is being undertaken).
d) To assess the
2.
Method of skin biopsy
Choose the biopsy site; if possible, select an area where the incision can
follow the normal skin creases. Infiltrate the area with local anaesthetic.
Using a sharp scalpel, excise an ellipse of skin. It should be at least 1 cm long.
The width, however, matters little; 2 mm is usually ample, and the thinner
the biopsy, the better the fixation. The incisions should be vertical, and
extend right through the dermis to the subcutaneous fat. To avoid tissue
distortion always handle the biopsy gently, and apply forceps at the corner,
not across the centre.
48
Do not allow the biopsy to dry; blot gently on gauze to remove blood; straighten
it, and immerse in fixative (see below). If the biopsy tends to twist up, straighten
it on a small piece of cardboard, and put it with the card into fixative.
Close the skin incision with suitable sutures.
In some circumstances a punch biopsy is more practicable than using a
scalpel; but unless punches are kept well sharpened they cause more
tissue distortion. Punch biopsies of 5 mm or less heal well without sutures,
and require a dressing for only a few days; this is often an advantage.
But such biopsies are too small for accurate histological classification; so
when such small punches are used take two biopsies close together.
To take a punch biopsy, apply gentle pressure and rotation to the punch
till it has penetrated to the subcutaneous fat; then remove the punch, lift
the biopsy gently with fine forceps, cut through the fat at the base of the
cylinder of tissue. Blot the biopsy gently to remove blood, and immerse in
fixative at once. Rinse the punch immediately in water to avoid blood
clotting in its lumen.
3.
Nerve biopsies
Nerve biopsies are normally only performed for research purposes. However,
they can be of value in patients suspected of early replased tuberculoid leprosy,
when the nerve may show evidence of active leprosy before new skin lesions
or deterioration of nerve function develop. They are also occasionally useful
to confirm the diagnosis in patients with enlarged nerves but no visible skin
lesions.
Full details of the technique of nerve biopsy are given in:"Changes in Sensory Acuity Following Radial Nerve Biopsy in
Patients with Leprosy". Brain 1971 94 43 (J.M.H. Pearson and
A.G.M. Weddell)
4. Fixation of biopsies from leprosy patients
The most suitable fixative for skin biopsies in leprosy(and othergranulomatous
skin diseases) is Ridley's Zenker-formol, the formula for which is given below.
After about 2 hours fixation in this fluid, the biopsy should be transferred to
70% alcohol, in which it may be kept indefinitely. 10% neutral formalin may
be substituted for 70% alcohol; being non flammable, it may be more
suitable if the specimen must travel by post.
49
Ridley's Fixative
Formaldehyde 40%
Mercuric Chloride
Glacial Acetic Acid
Distilled Water
10 ml
2G
3 ml
to 100 ml
This solution is stable; the fixative need not be made up from two solutions
at the time of use. However, if a sediment develops, pour the fixative gently
to avoid the sediment entering the bottle and contacting the biopsy; or remove
it by filtration.
5. Staining biopsy material from leprosy patients
The "TRIFF” stain has the advantage of demonstrating bacilli and tissues
together. Full details are given in:-
"An Improved Technique for the Histopathological Diagnosis and
Classification of Leprosy”. Leprosy Review 1965 36 1. (E.A.
Wheeler, E.G. Hamilton and D.J.Harman).
B. Biopsies for Mouse Foot Pad Inoculation
These biopsies are most commonly taken from patients suspected of deve
loping dapsone resistance.
1.
Preliminary Investigations
Chose 4-6 active looking skin lesions which are suitable for biopsy, and take
skin smears from them; check the Bl and Ml of each. Select for biopsy the
lesion with the highest Ml, provided the Bl is 4 + or more.
2.
1.
2.
Biopsy technique
Clean the skin very thoroughly.
Take the biopsy according to the normal procedure; but the biopsy should
be larger, about 15 mm long and 5 mm wide.
3. Blot the biopsy free of blood, then rub the cut edge on a clean microscope
slide, thus making an “impression smear”.
4. Put the biopsy in a clean, dry, sterile bottle, and seal it.
50
5.
Keep the biopsy at 4% C (in a refrigerator or on ice in a vacuum flask)
till it is processed. THE BIOPSY MUST NOT BE FROZEN.
6.
Before processing the biopsy check the Bl and Ml of the impression smear.
If either is low, the biopsy is unlikely to be suitable for mouse foot pad
inoculation.
3.
Transportation.
If the biopsy is to be processed elsewhere:a) pad the biopsy container with adhesive plaster to avoid a sharp edge
breaking the wall of the vacuum flask.
b) pack the vacuum flask in a well padded package, or suspend it on rubber
(old inner tube) strands in a small light weight crate.
A biopsy will only keep cool for 36 to 48 hours in a flask well packed with
ice. If transportation will take longer, arrangements must be made for it to be
re-iced en route. The mice should be inoculated within 5 days of taking the
biopsy.
4.
Inoculation from skin smears
Mouse foot pad inoculations can also be set up using skin smears from
active lesions. This technique has some advantages over the use of biopsies.
For details see:-
"A simplification of the mouse foot pad infection using Myco
bacterium leprae from skin scrapes" Lepr. Rev. 1975 46
105 (J.M.H. Pearson).
APPENDIX 3
Techniques of sensory testing
Sensory tests are performed for different purposes, but the technique is the
same though the stimulating object varies. The test stimulus must first be
demonstrated to the patient, with his eyes open, in a skin area without
anaesthesia. The patient is asked to point to the place touched by the tester.
The procedure is repeated, but with the patient’s eyes shut. Finally, sensatibn
in the relevant site is tested. In each case the stimulus object is touched
gently on the skin, as if sensation to pin prick were being tested.
1.
To determine whether there is sensory loss in a skin lesion that may be
caused by leprosy, use a piece of cotton wool rolled at one end to a fine
point. If the patient fails to feel the stimulus in the lesion, but feels it in
adjacent skin, sensory loss is present.
2.
To test for anaesthesia of the hands or feet, use, for the hands, a stiff
nylon bristle about 2 cm long mounted on wire, for the feet, the point of
a ball point pen. Touch firmly enough to bend the bristle slightly, or to
indent the skin of the foot slightly. If the patient fails to feel the stimulus,
the degree of anaesthesia is sufficient for him to be at risk of inadvertent
self injury.
3.
To follow the progress of neuritis, use serial tests every few weeks. Test
the relevant skin areas with nylon bristles of varying stiffness, and record
the softest one felt by the patient. Full details of this test, and precautions
needed if it is to give reliable results, can be found in:"Changes in sensory acuity following radial nerve biopsy in
patients with leprosy”. Brain 1971 94 43. (J.M.H.Pearson and
A.G.M.Weddell).
52
GLRA — DEVELOPMENT AND AIMS
German Leprosy Relief Association (GLRA), which financed the printing of this
small volume was founded in 1957, a non-governmental, interdenominational
organization which is contributing to the anti-leprosy campaign throughout
the world.
Since its foundation GLRA made available 203 Million DM for
— 496 leprosy centers, district and national programmes
— construction of hospitals, dispensaries and other accommodations
— research work and equipment
— training
Moreover, printing and propagation of technical literature on leprosy and in
formation about this disease in Europe and the endemic countries were
covered by these funds.
185 doctors, nursing staff and other experts worked for GLRA in the field of
leprosy; in addition there was/is a number of native doctors and other staff
being paid or receiving allowances from GLRA.
GLRA attaches great importance to a cooperation within the International
Federation of Anti-Leprosy Associations (ILEP), to the creation of which GLRA
made a considerable contribution.
GLRA aims at an integration of leprosy services into the public health service.
In consideration of its statute and according to the will of its benefactors GLRA
supports rehabilitation and resocialization projects and thus takes further care
of those leprosy sufferers, who as a result of the disease, are blind and
crippled and are consequently not accepted from society.
Acknowledgment.
The original photographs were taken by the late Dr. J. A. Kinnear Brown
53
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