The Classification of Pulmonary Tuberculosis and An Outline of Standardised Principles of Management pot

The Classification of Pulmonary Tuberculosis

and

An Outline of Standardised Principles of

Management

By
MILOSH SEKULICH

“
In

all science progress is the result only of a series of continuous efforts, often
ignored or unknown, and the pretended discoveries are only the continuation
or the consequence of facts acquired, but insufficiently known or wrongly
interpreted; the scientific prospectors are generally isolated, often repulsed,
even at the moment when the ensemble of workers follows them
and of ten forgets them.” Th. Tuffier, Paris, trans. Lawrason Brown, 1941.

Ever since the time of Hippocrates attempts have been made to classify tuber-
culosis. Not until the 19th century was a clear clinical division made between acute
and chronic forms (Fournet, 1839); later there was a tendency to describe these forms
as ‘galloping consumption’ and ‘consumption’; to-day they can be accurately described,
not only on clinical grounds, but pathologically, radiologically and pathogenetically
as ‘malig nant primary’ and ‘advance secondary’.

The first clinico-pathological classification was by Bard (1898, 1927). He
described four forms: parenchymatous, interestitial, bronchial, and post-pleuritic.
Bard postulated the still valid principle that every form must have ‘per son evolution,

son pronostic, sa marche generate, une veritable unite lui conferant la possession d’une
certain autonomic’. This system has survived until the present day, but owing to the
introduction of numerous morphological sub-forms, has become over-elaborated. It
remains confusing because it takes no account of pathogenesis.

The first pathological classification, based on a description of the pathological
lesions, was by Albrecht (1907). The lesions were divided into three groups: (1)
indurating, cirrhotic, healing, (2) nodular (productive), and (3) caseous-pneumonic
(exudative).

Another widely-adopted clinico-pathological classification was that of Turban
(1907). Here the basis was the quantitative extent of the lung lesions: three stages
were differentiated by physical signs. This system was supplemented by the radiologi-
cal findings to form the basis of the official British and American classifications. Two
further factors, the degree of activity, and sputum findings were introduced into the
British classification; in America many changes in emphasis and other details have been
made in the last 50 years, some of them being admittedly retrograde.

The first pathogenetic classification was that of Ranke (1916, 1919). He
believed that in its evolution tuberculosis, like syphilis, passes through three well-defined
stages.

Recently, Dufourt (1953) like New man (1930) has attempted to combine the
classification of Bard and Ranke. He believes that the ‘cycle of the infection’ can

Ind. J. Tub., Vol. IV, No. 4.
156 THE CLASSIFICATION OF PULMONARY TUBERCULOSIS
thus be expressed, but the fallacies of the Ranke classification make this attempt
confusing and unsatisfactory. Pathogenesis has been greatly advanced by Rich (1951)
and others since Ranke’s day.

It is pointless even to mention any of the other numerous classifications which
have been suggested. They are all deficient in some respect. I have tried many of them
during the past 35 years, and fail to give satisfaction.

What is wanted is an international classification with standardised terminology,
and one which would bring order into the present confused picture. This is one of the
pre-requisites for the compilation of comparable statistics from diverse areas. Is this
possible? I believe that with the vastly increased knowledge of tuberculosis available
to-day it can be done. It can now be based on the pathogenetic types of the disease,
its clinico-pathological forms, and the extent and degree of activity of the disease.
Such a global classification includes all those mentioned above, except Ranke’s which
is based on an erroneous hypothesis. It has been fully described in my books (Sekulich,
1953, 1955, 1956).

The Classification

My classification consists essentially of the following two types and four forms,
the latter of which can be subdivided into numerous subforms for clinical purposes;
only five subforms are required for epidemiological purposes; various particulars of
extent and activity are added according to the purpose in view.

1
. Primary Type

1. Inflammatory Form (Benign Primary)

2. Caseous Form (Malignant Primary)

2. Secondary Type

1. Fibro-caseous Form (Bronchogenic)

2. Fibrous Form (Haematogenous)

For
clinical
purposes the categories required are briefly outlined below:

I. Primary Disease :

1.
(a) Active Benign Primary—
This includes persons with a radiologically
invisible lesion but with a positive tuberculin reaction, and also those with a radiologi-
cally visible lesion, complicated sometimes by resolving pneumonia, atelectasis, or
pleural effusion;

(b) Quiescent Benign Primary—
including those with a calcified nodule or
round focus or no residual lesion, absorption having been completed.

2. (a)
Active Malignant Primary—
this has serious subforms, lobar caseous
pneumonia, bronchopneumonia, or acute miliary tuberculosis;

(b) Quiescent Malignant Primary
—characterised by calcified nodules or round
foci or again, no residual lesion.

It is only after primary disease, in one or other of these forms, has become
quiescent that secondary disease can arise, either by a new exogenous infection (in appro-
ximately 70 per cent) or by autogenous reactivation (in about 30 per cent).

Ind. J. Tub., Vol. IV, No. 4.

MILOSH SEKULICH 157

II. Secondary Disease

1. (a)
Active Fibro-caseous Form—
This includes unilateral and bilateral
minimal, moderately advanced and advanced disease, as well as abortive tuberculosis;
(b)
Quiescent Fibro-caseous Form—
including residual lesions, calcified or round foci,
and no visible residual lesion (complete absorption).

2. (a)
Active Fibrous Form—
including localised and disseminated chronic
miliary disease, localised and diffuse fibrous tuberculosis with emphysema, fibrocavi-
taria, fibrous tuberculosis of all these forms with dissemination (usually a terminal
event);—including localised or disseminated calcified nodules, hard fibrosis, round
focus, and residual sclerosis.

The extent of the lesion
should be defined by zones, that is upper, middle, or

lower zone or a combination of these.

The degree of activity
should be described in the following terms active, pro-
gressive, stationary, regressive or inactive, quiescent, arrested, recovered.

For epidemiological
purposes only 9 categories are needed:

I.—
Active forms:
(1) benign primary; (2) malignant primary; (3) minimal
secondary; (4) moderately advanced secondary; (5) advanced secondary; (6) fibrous
secondary; (7) fibrocavtaria secondary; (8) non-pulmonary.

II.—
Quiescent forms:
residual lesions of any of the above.

History of the Classification

When I commenced work on tuberculosis in the year 1923 active and healed
primary tuberculosis had already been described by Parrot (1876) , Kuss (1898), Ghon
(1912, 1916, 1923) and others. The calcified primary complex (Ranke 1916, 1919)
was often observed in autopsies of persons dying from other causes than tuberculosis,
and the active stage of benign primary disease ending with a calcified primary complex
was diagnosable by serial radiographs. In autopsies in children we frequently saw
active progressive forms (acute miliary tuberculosis, lobar caseous pneumonia and case-
ous pneumonia and caseous bronchopneumonia). It was gradually realised that these
were always associated with unilateral caseous hilar lymphatic nodes and with almost

complete absensce of fibrosis. Similar findings were observed also in autopsies of young
adults who had recently come to the town from the mountains.

An apparently similar but pathologically different autopsy picture, however,
was commonly encountered in other adults but never in infants. In this latter picture,
caseous hilar nodes were absent and fibrosis was conspicuously present, especially in
the form of cavities with a thick fibrotic wall. These two superficially similar, but
essentially different, findings in autopsies always corresponded to two quite different
clinical histories, especially as regards the duration of the disease. The first was invari-
ably fatal within a few months and always in less than a year, while the second was
usually of several years’ duration, ending in an acute phase lasting several months.
Accordingly, on the basis of the duration of the disease in life, I began to classify these
two clinico-pathological syndroms as ‘acute’ and ‘chronic’ types of the disease respecti-
vely. Later, when it was found that the second form often exhibited a calcified primary
complex, the conception of ‘primary’ and ‘secondary’ tuberculosis as two distinct types
corresponding to ‘acute’ and ‘chronic’ came into my mind.

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158 THE CLASSIFICATION OF PULMONARY TUBERCULOSIS
Since the acutely fatal primary type above mentioned was obviously very differ-
ent clinically and pathologically from the naturally healing benign primary complex,
the idea arose of two contrasted forms of the primary type, which were termed ‘benign’
and ‘malignant’ respectively.

The conception of the two forms of secondary disease (fibro-caseous and fibrous)
was only reached after several years’ pointed study of serial radiographs. At this time
the Assman focus (1925, 1930) and Simon foci (1930) had already been described, but
the evolution of the secondary type of the disease was not clear. Collapse therapy
and improved rest treatment were now resulting in numerous cases of healing and healed

secondary disease. Serial radiographs in such regressive cases often showed, after
some years, lesions somewhat similar either to a unilateral Assman focus or to bilateral
Simon foci. This observation of the course of regression led me in many instances to
imagine that a similar but reversed course must have been followed during the evolution
or progressive stage of the disease. I therefore gradually acquired the habit of placing
serial radiographs in reverse order, from the healed lesion back to the advanced stage.
The course of evolution and involution of the active lesions, as radiographically always
appeared to follow the same route but in opposite directions. It gradually became
apparent that regression in secondary disease, ended in two different ways, (1) with a
unilateral lesion similar to the Assman focus and (2) with a bilateral apical lesion some
what similar to Simon foci. At this stage it was becoming fairly clear to me that in the
secondary type of the disease there were two distinct forms, which could be correctly
described as ‘fibro-caseous’ and ‘fibrous’ disease respectively.

The late results of collapse therapy and early results of chemotherapy contribut-
ed new facts regarding the process of regression of the disease, and regarding arrest of
the process of progression at an earlier stage than had previously been seen. From
the facts thus collected, it became clear that all four forms of the disease exhibited a
similar but reversed course during these two phases. It then seemed reasonable to
described this process as a general ‘law’. This principle was formulated as ‘the law
of evolution and involution in tuberculosis’. The pathological processes involved in the
two phases, progression and regression, are of course, different. In the developing
lesion there is perifocal reaction, exudation, caseation, liquefaction and destruction of
tissue. In the regressing lesion (apart from that ending in complete absorption) the
reparatory forces of fibrosis, calcification, sclerosis, cellular regeneration, compensatory
emphysema, etc., all help to close the gap partially or completely. But it is regularly
observed both pathologically and radiologically that the most recent active associated
lesions are absorbed or healed first in the process of regression and the ‘original’ (pri-
mary) or ‘initial’ (secondary) lesions last; and by observation of the process of regres-
sion in uncomplicated cases we are finally led back to what was the original or initial

lesion of the disease. When we compare serial radiographs showing regression towards
complete absorption with serial radiographs showing progression, we see exactly the
same picture in reverse. In cases, however, which in the process of regression leave
residual lesions, we have to ignore the scarring of the associated foci and, when this is
done, we see again exactly the same picture in reverse.

The crucial clinical demonstration of the truth of this law is to be found in the
study of a large series of cases (I have personally observed several hundreds) in which
the course of the primary type of the disease was observed from activity to quiescence,
and in which, after a varying interval of months or years, the secondary type of tuber-
culosis appeared, developed and regressed to quiescence. After this study I was at
last convinced that the natural history of pulmonary tuberculosis was indeed governed
by this law, and the outline of my classification logically followed. It appears to be the
key to the solution of most problems of diagnosis, management and epidemiology
in tuberculosis. It also provides the only yardstick which I have found reliable for
comparative measurements in all branches of tuberculosis.

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MILOSH SEKULICH 159
Pathogenetic Basis of the Classification

My classification was primarily based on clinical and pathological study of many
cases over long periods of years. It has now been found that the deductions then
made, purely from clinical and pathological data, are neatly supported by a
reasoned consideration of the complex operation of Rich’s five fundamental factors
of influence in the pathogenesis at each and every stage of the disease.
The five fundamental pathogenetic factors are:

I. Quantity of pathogenic tubercle bacilli

II. Virulence of the infecting bacilli

III. Natural resistance

IV. Acquired resistance

V. Hypersenisitivity

These factors determine the
pathogenetic type
and form of the disease. Certain
physiological and accidental factors may greatly influence the
establishment
and
develop-
ment
of the disease. Such physiological factors include heredity, sex and age; the acci-
dental factors include malnutrition, physical and mental overstrain, intercurrent infec-
tions, trauma, occupational risks, endosrine disturbances, alcoholism, etc. These
factors cannot determine or change the
type
of the disease, although they may modify
its form and influence its extent and activity.

The extent and activity of the lesions vary directly with three of the funda-
mental factors of pathogenesis, quantity of bacilli, virulence of bacilli, and hypersensiti-
vity; and they vary inversely with the two fundamental factors, natural and acquired
resistance. The greater the quantity and virulence of the bacilli and the higher the
degree of hypresensitivity the larger and more destructive will the lesions be; while

the various degree of natural and acquired resistance will exercise their influence in
the opposite sense, thus restricting the multiplication of the bacilli and the progression
of the lesion.

Mechanism of the Primary Disease

When tuberculous infection is first established in the previously uninfected
body the tissues react at the beginning as they would against many kinds of implanted
foreign material, namely with hyperaemia, infiltration of polymorphonuclear leuco-
cytes and exudation of fluid, and later with mononuclear cell emigration; if this process
extends to tubercle formation or an area of infiltration a ‘lesion’ may be said to have
began. During this early period the host factor opposing the growth of the bacillus
is natural resistance only, and this is insufficient to prevent the tubercle bacilli from
multiplying and spreading to the regional lymphatic node and blood stream, thus produ-
cing hilar node infection in the case of the lungs, and
pre-clinical bacillaemia.
It is
only when acquired resistance appears that a significant change occurs, the lesion taking
on the characteristics of primary tuberculous disease. From this point the ‘original
lesion’ develops in one of two ways, depending on the relative potency of the infecting
dose on the one hand and the degree and rapidity of development of acquired resistance
on the other.

The dose of bacilli implanted by inhalation is usually small, having been esti-
mated to be between 1 and 400 bacilli per droplet. This dose may multiply, however,

Ind. J. Tub., Vol IV, No. 4.

160 THE CLASSIFICATION OF PULMONARY TUBERCULOSIS
into a large quantity of bacilli before the appearance of acquired resistance if the latter

is delayed. In contrast, when acquired resistance develops rapidly and strongly, the
multiplication of bacilli is suddenly stopped, reparative changes of fibrosis limit the
spread of the lesion, and encapsulation begins. This is the characteristic lesion of the
benign primary complex, which is much the most common of the two primary forms of
the disease. If acquired resistance, however, is delayed and weak, the bacilli in the
infecting dose multiply geometrically during the preliminary period of natural resistance
only, and by the time that the spreading inflammatory lesion begins to be checked by
acquired resistance it already occupies a relatively large area. From this time ‘the origi-
nal lesion of primary disease’ takes on the characteristics of the malignant primary
complex, which is the second and much rarer form of primary tuberculous disease in
man.

The appearance of acquired resistance is closely followed by the appearance
of hypersensitivity in both forms. This is at first more a liability than an asset. In the
benign primary form where the original lesion is small and is being rapidly localised by
fibrosis, the reaction produced by hypersensitivity is mainly a perifocal inflammation of
very variable degree. In fact this perifocal inflammation of the benign primary complex
varies from almost nothing to a large pulmonary inflammation of the lung, with or
without pleural effusion. In the case of the malignant primary complex the effect of
hypersensitivity is exerted on the lesion itself which is unprotected by significant fibrosis.
Here hypersensitivity actually destroys such fibrosis as is present and encourages necrosis
and caseation, and consequently further extension of the original lesion and dissemina-
tion. Hence the malignant primary form is characterised predominantly by caseation
in the original lesion and in its regional node as well as in their associated foci.

Occasionally malignant primary disease showing bronchopneumonia or acute
disseminated and generalised miliary tuberculosis may arise by an accident from a
benign primary complex so located as to allow discharge of a caseous mass into a bron-
chus or a blood vessel. Here the factor of ‘quantity of bacilli’ effectively overbalances
the acquired resistance present and produces similar effects to that of a natural exending

malignant primary complex.

The benign primary form, being characterised by a perifocal inflammatory
reaction is, with its subforms, termed the
inflammatory form
although there may be
some caseation in the focus or lymph node. The malignant primary complex, being
characterised predominantly by caseation, is, with its subforms, termed the
caseous
form.

The evidence in favour of these developments is partly derived from animal
experiments and partly from numerous clinical observations in man. In animals the
influence of the factors ‘quantity of bacilli’ and hypersensitivity are easily demonstrable,
but laboratory animals do not exhibit acquired resistance to such a degree as man.
These animals succumb in about six months to the smallest dose of tuberculous infec-
tion, while in man most of the infected survive with primary disease which becomes
quiescent in six to twelve months. There is no other obvious explanation of this
difference than the ability of the human being to develop and maintain acquired resis-
tance. In not more than 5 per cent of children under two years seen at Chest Clinics
in England does acquired resistance fail; in these cases the malignant primary complex
develops, although there is no reason to suppose that the infective dose inhaled is
usually different from that inhaled by children with the benign primary complex.

Benign primary tuberculosis
consists of the benign primary complex with its
associated lesions. The benign primary complex consists of a primary focus and its
tuberculous regional lymphatic node. It may be associated with a small or large perifo-
cal inflammation and it is nearly always unilateral, the bilateral primary complex being

Ind. J. Tub., Vol. IV, No. 4.

MILOSH SEKULICH 161

an exceptional finding (some 2 per cent). It may be complicated by resolving tuber-
culous pneumonia or atelectasis, or a combination of these, or by pleural effusion, or
occasionally by meningitis or other non-pulmonary metastases. When this disease
heals it is either completely absorbed or leaves a residual encapsulated caseous focus,
or a calcified nodule, or a scar, or a round focus (about 2 cm. diameter), and a healed
or calcified lymphatic node; sometimes there are also a few neighbouring or distant
calcified foci and more frequently a few symmetrical bilateral, apical foci. After a
period of quiescence, reactivation may occur, rarely, giving rise to the minimal lesion
of secondary tuberculosis (about 5 per cent of minimal lesions), but more frequently
to the localised chronic miliary form (about 25 per cent of the fibrous forms) and to non-
pulmonary forms of secondary disease.
Exogenous
secondary infections, however,
follow much more commonly after a short or sometimes a long, period of quiescence,
giving rise to the unilateral minimal lesion (in about 70 per cent of these cases). The
remainder proceed to complete healing and immunity which is permanent in the vast
majority of benign primary cases.

Malignant primary tuberculosis
consists of the malignant primary complex,
namely that expanding type of primary complex in which the original caseous pneumo-
nic focus progresses, sometimes cavitates (primary cavity), and exhibits no tendency
towards encapsulation. It is always associated with multiple caseous lymphatic nodes.
In its evolution it may be complicated by lobar caseous pneumonia, caseous broncho-
pneumonia and disseminated or generalised miliary tuberculosis. When these lesions
heal, complete absorption is possible only if they have had early chemotherapy and other

treatment. The residual lesions include multiple fibrous scars or multiple calcified
nodules or multiple encapsulated foci, and rarely a single quiescent focus,

Mechanism of Secondary Disease

In the previously infected body in which the primary disease has become quies-
cent or healed, established infection may again take place in exactly the same way as in
primary disease, or may occur by reactivation of the primary disease. But here the
established infection is usually initiated in the presence of hypersensitivity and of slight
residual acquired resistance. This has an immense influence on the development of the
‘initial lesion of secondary disease’ after the stage of established infection; and this
lesion at once begins to show quite different characteristics from those of the ‘original
lesion of primary disease’. The initial tissue reactions of hyperaemia, infiltration,
exudation and tubercle formation (area of inflammation) are more rapid and acute,
but checked at an earlier stage than in primary disease under the influence of acquired
resistance (Koch’s phenomenon). Spread to the regional lymphatic nodes is almost
completely prevented and bacillaemia is neutralised or immediately checked by the
acquired resistance rapidly recalled and present at an earlier stage. For the same
reason fibrosis is rapidly developed in the lesion, and is present side by side with some
degree of caseation, which develops under the influence of the hypersensitivity. From
this point the initial lesion of secondary disease develops in one of two directions;
(1) that of unilateral fibro-caseous disease, with characteristic bronchial spread if
progressing, or (2) that of bilateral symmetrical fibrous disease, spread through the
blood stream. The unilateral fibro-caseous form is characterised by a mixture of case-
ous and fibrous elements, frequently associated with inflammatory reactions, and steadily
progressing without significant involvement of the regional lymph nodes (‘minimal’,
‘moderately advanced’ and ‘advanced’ fibro-caseous disease with or without caseous
dissemination). The bilateral fibrous form is characterised mainly by fibrous nodules
(caseation being very slight) or by patches of infiltration. These are situated bilaterally
in the apices, and extend slowly downwards (localised chronic miliary tuberculosis

and other subforms including fibrocavitaria).

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162 THE CLASSIFICATION OF PULMONARY TUBERCULOSIS
Fibro-caseons Form

The minimal lesion is the initial lesion of this form. It is a small asymmetrical
unilateral secondary lesion commencing with a few tubercles or small area of inflamma-
tion or both. In its course it has a strong tendency to develop caseation and fibrosis
concomitantly (in contrast with untreated malignant primary disease). It is of relatively
chronic destructive type, spreading and disseminating mainly by the bronchial route,
and may progress through three stages from ‘minimal’ to ‘moderately advanced’ and
‘advanced’ phthisis. At any of these stages it may be complicated occasionally by
sudden limited or widespread caseous dissemination, although far less regularly than in
malignant primary disease. The reverse process of regression and healing over a
period of time can regularly be observed in treated cases by means of serial radiographs,
and it is then constantly found that a similar but opposite course to that of progression,
is followed from ‘advanced’ through ‘moderately advanced’ to ‘minimal’ and finally to
the residual lesion or lesions. The residual lesions of the fibro-caseous form are scars,
calcified nodules or one of more round foci.

Fibrous Form

The initial lesion of the fibrous form, localised chronic miliary tuberculosis,
is characterised by symmetrical multiple small tubercles or small discrete areas of
inflammation usually situated in both upper zones. They may sometimes be radiologi-
cally invisible until they have healed. They arise not by inhalation but by
reactivation
and haemic spread to produce the following types of lesions: (1) disseminated chronic

miliary tuberculosis, (2) localised fibrous tuberculosis with emphysema, (3) diffuse
tuberculosis with emphysema, and (4) fibrocavitaria—the form in which cavitation
occurs typically within a caseous focus (such as a ‘round focus’) and not by caseous
extension. An occasional development, usually terminal, is fibrous tuberculosis with
caseous dissemination. When the fibrous form heals it ends in localised calcified nodules
(mostly in the upper zones), disseminated calcified nodules, or residual fibro-sclerosis,
and occasionally by absorption. Their initial localisation is symmetrical and, in nearly
100 per cent, in both upper zones. This applies both to the active and quiescent stages.

In its symmetrical distribution from onset, its development symmetrically
downwards, its prolonged course, relative absence of bronchial spread, generally small
element of caseation and prominent fibrosis, it has a natural history quite different from
that of the fibro-caseous form, although it produces occasionally localised reactivation
and cavitation. It differs even more from primary disease. (It should be noted that
mere cavitation is not in itself sufficient to assign a case to the fibro-caseous form).

Localisation

A marked difference is demonstrated by clinical observation between the localisa-
tion of the
original
lesion of primary disease and that of the
initial
lesion of secondary
disease. In primary disease, both benign and malignant, the original lesion was establi-
shed in the middle and lower zones taken together in approximately 80 per cent
of my series cases; while in secondary disease the initial was established
in the upper zone in over 80 per cent (Sekulich, 1955). Here is an outstanding difference
between the respective localisations of the first lesion of primary and that of secondary
disease.

In explanation of the localisation of the first lesion of primary disease in the
absence of acquired resistance and hypersensitivity, we have to search for mechanical
factors. As the predominant localisation of the original lesion of primary disease in
man is in the midzone (in 50 per cent of cases) it would seem that the larger infected

Ind. J. Tub., Vol. IV, No. 4.

MILOSH SEKULICH 163
droplets gain access to this area for mechanical reasons more readily than to other parts
of the lung.

The apical localisation of the initial lesion of secondary disease seems to be
strikingly associated with the presence of a lower degree of acquired resistance (or possi-
bly a different degree of hypersensitivity) in the apex than in other parts of the lung. The
real issue is, however, still undetermined, namely what is the mechanism by which acquir-
ed resistance (or hypersensitivity) so influences localisation that it becomes predomina-
ntly apical in secondary disease.

Summary and Conclusions
Primary and secondary tuberculosis are two distinct types of the disease, with
an entirely different natural history, onset, character and localisation of the lesions,
course and termination. In their progression and regression they are, however, govern-
ed by the same law—’law of evolution and evolution in tuberculosis’. There are two
distinct original lesions in primary tuberculosis, the benign and the malignant, and two
distinct initial lesions in secondary tuberculosis, the unilateral minimal lesion and the
bilateral localised chronic miliary tuberculosis, and these lead respectively to the fibro-
caseous and
fibrous
forms of secondary disesase. The following are the chief criteria

of differential diagnosis of the primary from the secondary type of the disease.

Primary Disease
1. Recent tuberculin conversion (3 to 8 weeks previously).

2. Radiological evidence of the primary complex or enlarged hilar lymphatic
node.

3. Localisation of the original lesion. It is in the middle zone in about
50 per cent of cases, and in the lower and upper zones in about 25 per cent each.

4. Recent normal radiograph prior to the development of the lesions.

5. Characteristic evolution and involution of primary disease, including
especially the tendency to caseous dissemination in malignant primary tuberculosis.

Secondary Disease

1. Radiological evidence of a healed primary lesion prior to the appearance
of the new lesion or concurrent with it.

2. History of tuberculin conversion and clear lungs of at least a year’s duration.

3. Absence of fresh macroscopic involvement of regional lymphatic nodes.

4. In the fibro-caseous form, the typical unilateral minimal lesion usually in
an upper zone (about 90 per cent), and in the fibrous form, localised chronic miliary
foci in both upper zones (about 100%).

5. Relatively slow progression and only occasional dissemination in compari-

son with malignant primary disease; progression more rapid and bacillaemic metasta-
ses almost absent in the fibro-caseous form as compared with the fibrous form.

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164 THE CLASSIFICATION OF PULMONARY TUBERCULOSIS
6. Characteristic different course and termination of secondary tuberculosis,
as compared with primary; regression ultimately to the minimal lesion in the fibro-
caseous form and localised chronic miliary foci in the fibrous form, finally ending in
residual lesions in both forms with their characteristic localisation.

The Principles of Management

Management of tuberculosis, as employed to-day, is largely empirical, and a
physician is greatly handicapped by the absence of standardised methods of approach,
based logically on fundamental principles. If the fundamental principles of pathogene-
sis are understood and a ‘complete diagnosis’ is made on the basis of type and form of
the disease as well as extent and activity, then management can be prescribed with a
feeling of satisfaction by any practitioner. It should be clearly reconginsed, however,
that a correct classification is the key to correct and standardised principles of
management; and that only with standardised principles of management can results
in various series and in various countries be compared to best advantage and the
knowledge derived therefrom adapted to general use.

There is ample evidence that
M. tuberculosis
has not changed its virulence and
pathogencity for centuries; that there is no change in the natural history of the two
types and four forms of pulmonary tuberculosis. What is persistently changeable,
is the distribution of cases of the two types and four forms. There are certain parts in

the world, into which
M. tuberculosis
has never penetrated, and on the other extreme
there are certain areas in the Middle West and North West of the United States, where
tuberculosis has almost disappeared, tuberculin positives in young adults being less
than 10 per cent. Between these two extremes there are numerous degrees. For
instance, whilst in South Africa malignant primary disease is on the increase, in England
this form is becoming rare. Any change that occurs is not in the character of the disease,
but in the epidemiological picture, arid this varies according to the prevalence of the
factor of infection on one hand and the factor of resistance on the other. These two
factors are the essential elements in an epidemiological classification. They must be
clearly distinguished, and this can only be accomplished when the cases concerned
are classified to primary and secondary types and the four main forms of the disease.
In the management and rehabilitation of a case, and especially in epidemiological work
physiological and accidental factors play a very important part in resistance.

In all forms of pulmonary tuberculosis the essential approach to management
is to distinguish the original primary or the initial secondary lesion (which are the first
to start and the last to heal) from their associated foci. By rest treatment and chemo-
therapy we firstly attack ‘and heal the associated lesions. Sometimes all the lesions,
the original or initial and associated foci, are controlled by short or prolonged chemo-
therapy. When, however, the original or initial lession is not brought to quiescence,
mechanical or surgical means of dealing with it are needed.

When considering collapse therapy or resection at least four factors are of
importance: (a) pleural thickening or obliteration, (b) bronchial involvement, (c) the
age of the patient, and (d) the social and environmental factors.

There is clear evidence that benign primary tuberculosis with or without rest
treatment heals naturally either by complete absorption or calcification. This also is

the case, although much less frequently, in minimal and localised chronic miliary second-
ary tuberculosis. For the former approximately a year is needed for quiescence; for
the latter at least two years. When the primary disease is healed, secondary disease
develops in a small minority of cases, but true relapse of healed secondary disease is
very rare.

Ind. J. Tub., Vol. IV, No. 4.
MILOSH SEKULICH 165

Rest treatment remains as important as it has ever been. It, of course, includes
graded exercises and even light work. It is a mistake to depend upon chemotherapy
alone without rest treatment; this leads to the use of prolonged chemotherapy instead
of the preferable short courses and it leads more often to the use of collapse therapy or
resection.

From past experience we know that artificial pneumothorax and pneutnoperi-
toneum acted mostly against the associated foci, and that the original and initial lesions
were rendered quiescent only after years’ of control (functional rest) and building up of
the body’s resistance. Even then there was need for further collapse therapy in the
form of thoracoplasty or plombage, or resection. To-day the use of artificial pneumo-
thorax and pneumoperitoneum is almost discontinued because a more powerful method
has appeared, chemotherapy. This does not mean that it is wise to dismiss these two
methods altogether; they may still be useful to shorten the course of chemotherapy or
in drug resistant cases.

An Outline of Standardised Principles of Management

I. Benign Primary Tuberculosis

1. The cardinal principle here is rest treatment for all active cases.

2. The only complications for which chemotherapy is indicated, are tubercu-
lous meningitis, tuberculous endobronchitis, and non-pulmonary tuberculosis.

3. Benign primary tuberculosis complicated with pleural effusion occasionally
requires aspiration of the fluid for mechanical reasons in addition to rest treatment.

4. Quiescent benign primary disease complicated with a round focus or with
bronchiectasis requires preventive or therapeutic resection, in particular cases.

Building up of the body’s resistance and life immunity are here the main aim
of rest treatment.

II. Malignant Primary Tuberculosis

1. Early diagnosis and prompt treatment is particularly indicated in these
forms owing to their rapidly progressive character.

2. Rest treatment alone is insufficient in contrast with the management of the
benign primary complex.

3. Rest treatment and prompt chemotherapy are the immediate indication,
and these should be carried on for several months or years until the lesions are rendered
quiescent. In early diagnosed and some advanced cases the original and associated
lesions may be healed by chemotherapy alone. In far advanced cases, however, the
associated lesions may be ‘cooled’ or rendered regressive. When this has been accom-
plished a suitable form of collapse therapy is usually required. Treatment in this order
greatly reduces the need for bilateral collapse therapy, other than PP. The most suit-
able initial form of collapse therapy is usually PP. even when the visible lesions are
unilateral, since associated foci on the other side may be present but invisible. All

forms of collapse therapy should be directed towards the ultimate control of the original
lesion. When the latter is regressing the associated foci will heal spontaneously under
the influence of the relatively high level of acquired resistance which has been built up.
For this reason it is of the utmost importance that the side of the original lesion should

Ind. J. Tub., Vol. IV, No. 4.

166 THE CLASSIFICATION OF PULMONARY TUBERCULOSIS
be identified. If treatment is applied correctly in this order the collapse measured
required in most cases will be reduced to PP in the majority, followed, if necessary,
by phrenic crush or AP on the side of the original lesion. Major surgery should rarely,
be required for caseous form treated correctly in this order.

In contrast, therefore, with benign primary disease (which generally requires
rest alone) malignant primary disease requires rest, prompt chemotherapy and sometimes
at a later stage collapse therapy, mainly PP. This is so, even in the cases which show
apparent complete absorption of the lesions, for two reasons: (1) some of the lesions
though invisible may be still active, and (2) collapse therapy, applied after about three
months’ chemotherapy, shortens the remainder of the course of chemotherapy and
speeds up the closure of visible as well as invisible cavities.

An exception may be made in the case of children, who, as a rule, are unsuitable
subjects for collapse therapy. In children, rest and chemotherapy may be and usually
are, except in late cases, sufficient to bring quiescence, but the occasional failures in
whom a residual cavity is evident, should be treated by resection. Resection of the
affected lymph node when the original focus has been rendered quiescent does not
to be justified.

Acute Miliary Tuberculosis:
Both the disseminated and the generalised type

require prolonged rest treatment and prompt chemotherapy which may last for months
and even for a year or two. Frequent routine examinations should follow in every
case for many years. Its non-pulmonary complications should be treated as in other
forms.

III. Fibro-caseous Form

Minimal Lesion:
Every case of minimal lesion should be treated. It seems that
the most rapid method of treatment is rest and chemotherapy which may or may not
be followed by collapse therapy. If collapse therapy becomes indicated it should follow
rest and chemotherapy. Major surgery is even less justifiable.

Moderately Advanced Disease:
Moderately advanced disease should be treated
actively in every case. The most rapid and successful management in general is rest
combined with chemotherapy which may be followed by collapse therapy, and even
major surgery in particular cases. Untreated moderately advanced disease is liable to
progress into advanced or bilateral fibro-caseous forms.

Advanced Disease:
Advanced disease should be treated actively in every
case. The most rapid and successful management in general is rest treatment together
with chemotherapy which may be frequently followed by collapse therapy if possible
or major surgery. The latter is more frequently required than in other forms of fibro-
caseous disease.

Bilateral Fibro-caseous Disease:
In bilateral fibro-caseous disease the most
rapid and successful management in general is by rest combined with chemotherapy in

the initial stage, followed by collapse therapy or even by major surgery in particular
cases. When the associated foci in the opposite lung to that of the initial lesion are
absorbed or cooled, the cases should be treated for a short time bilaterally with PP and
then in the way already described for the unilateral fibro-caseous form. In bilateral
fibro-caseous disease, therefore, bilateral collapse therapy is necessary only in cases in
which rest treatment and chemotherapy have not been sufficient to cool the associated
foci in the opposite lung. In cases where the initial lesion has been put under control to
quiescence of the associated foci, the latter usually heal naturally under the influence of

Ind. J. Tub., Vol. IV, No. 4.
MILOSH SEKULICH 167

acquired resistance. (This was observed in the past when thoracoplasty was performed
soon after the diagnosis was made. As soon as thoracoplasty has controlled the initial
lesion the associated foci tended to become absorbed or calcified). To-day major surgery
is performed almost invariably only on the initial lesion after the associated foci have
been cooled by rest and chemotherapy; alternatively, however, an operation is some-
times performed during three regressive phase and under cover of chemotherapy.
Empirical treatment of 101 cases of bilateral fibro-caseous disease showed that of 87
cases in which collapse therapy was performed, it was unilateral and almost invariably
against the initial lesion in 34 and was bilateral in 53 cases (Sekulich, 1955). In the latter
it was maintained for a much shorter period on the associated lesions, then on the initial
lesion. In all cases, except one, in which major surgery was performed the operation
was on the initial lesion. This group of cases of bilateral fibro-caseous disease is there-
fore highly instructive as to the true principles of management. These should be based
on the law of evolution and involution, and in general, on the natural history of the
disease. The initial lesion must always be distinguished from the associated foci, and
the appropriate measures taken accordingly.

IV. Fibrous Form

1. The active fibrous form should be treated by rest, and this may be sufficient
provided that it can be prolonged for two years or more.

2. The period of activity is shortened by combining chemotherapy with rest
treatment.

3. A considerable number of cases of the fibrous form can become quiescent
without collapse therapy.

4. Collapse therapy following rest and chemotherapy does, however, further
shorten the period of activity. It must, however, always be applied bilaterally, even in
fibrocavitaria when a visible cavity is present only on one side.

5. In the fibrocavitaria form, collapse therapy is nearly always indicated follow-
ing rest and chemotherapy.

6. The presence of pulmonary emphysema is characteristic of certain of these
forms, and does not contraindicate collapse therapy in the form of pneumoperitoneum.
On the contrary PP is beneficial in these cases, providing that over-exertion is avoided.

In conclusion it should be emphasised that the control or eradication of tuber-
culosis in any country depends mainly upon the maintenance of a good standard of liv-
living, in other words controlling what is called here the ‘physiological and accidental
factors’.

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ASSMANN
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