Диссеминированный туберкулез легких.

4. Disseminated TB.

4.1. Determination.
Disseminated or diffuse pulmonary TB is a generalized disease most commonly localized in the
pulmonary system. The rapid dissemination is well known as miliary tuberculosis and acute
generalization, but the chronic metastasizing form is more frequently recognized. Chronic
disseminated tuberculosis is defined by us when the disease is prolonged and involves several
organs of the body. Its typical characteristic is extension of focal, infiltrations and cavitary changes
amidst more than 3 segments in one or two lungs and more pronounced clinical and laboratory
manifestations than in small forms. Besides they may have sclerosis changes are more or less
expressed. It may arise both in primary and post primary TB infection.
4.2. Motivation.
Knowing of this form is necessary to every doctor to timely detect and prevent their progression
into different advanced forms.
4.3. Epidemiology.
By definition of both in primary and post primary TB infection means a new disseminated
tuberculosis may be both in children and in adults from an outside and inside source of infection.
Thus plays a role exogenous or endogenous source. In its broader interpretation, reinfection
tuberculosis refers to a pattern of disease that develops characteristically in adults who have usually
but not necessarily been infected previously. It implies a pattern of behavior of pulmonary lesions
often observed roentgenographically and characterized pathologically by limitation to the lung; by
progression with caseous sloughing, intrabronchial spread, and cavity formation; and by regression
with resolution of exudates, fibrosis, absorption, hyalinization, or calcification of caseous foci. All
stages of repair and progression may be seen together within the same lung, and lymph node
involvement is seldom extensive.
So, disseminated tuberculosis is a form of tuberculosis that is the result of Mycobacterium
tuberculosis travelling to different parts of lung, and besides liver, spleen and kidneys. Although it
is well understood that the bacteria spread from the pulmonary system to the lymphatic system and
eventually the blood stream, the mechanism by which this occurs is not well understood.
Patterns of progression and dissemination. For clinical diagnosis the extent of the pathologic
changes in the tissue must be of sufficient magnitude to reach the point of clinical or
roentgenographic detection; beyond this the behavior of the lesions is more readily observed. The
mechanisms by which extension and worsening occur are similar below as well as above this
threshold of clinical recognition. Dissemination is a term that applies directly to tubercle bacilli, and
extension or spread to progression of the lesions. They are considered together.
Direct extension is very rare. The intensity or extent of the original exudative component is
in proportion to the number and virulence of tubercle bacilli, the vascularity of the involved tissues,
and the susceptibility of the infected subject
Ductal or intracanalicular dissemination is more often. The new foci are usually of a lobular
distribution and often conform to the bronchopulmonary segments as seen on the roentgenogram.
They vary in size, age, and appearance and may be so extensive as to involve an entire lobe.
Lymphogenous dissemination. The great number of lymphatic channels in the lung provide
ample opportunity for dissemination of tubercle bacilli by this route. Lmyphogenous spread is more
frequent and extensive in primary tuberculosis in children. New lesions are commonly formed along
the lymph vessels but are more conspicuous in the lymph nodes, where larger numbers of bacilli are
found. Eventual access of bacilli to the bloodstream may occur by way of the lymphatics. It is
thought to occur for the most part in children or in persons with little immunity to the disease.
Lymphatic dissemination is often responsible for pleural involvement and lesions in the chest wall,
in the spine, and in the small bowel and abdomen.
 Hematogenous dissemination is the predominant way of granuloma scattering in the cases
with disseminated tuberculosis. Tubercle bacilli may be carried into the bloodstream in various
ways. Careful anatomic studies by Weigert have shown that diffuse tuberculosis, which usually
results from massive sudden bacterial dissemination into the blood, arises frequently from the
rupture of liquefied caseous material into a pulmonary vein, often from tubercles in the wall of the
vein. Other sources are caseous mediastinal lymph nodes, usually in primary tuberculosis or
caseous foci in extrapulmonary organs. Hematogenous seeding of more limited extent is recognized
as a frequent characteristic of primary tuberculosis in children, and it also occurs as a terminal event
in patients dying of tuberculosis.

4.4. Symptoms and physical signs.

Most cases of disseminated tuberculosis are diagnosed as the result of the patient feeling unwell and
so coming for help to a health center, a clinic, a hospital or a private doctor. Cough and sputum is
very common everywhere. Much of this is due to acute respiratory infections and lasts only a week
or two. In many countries there is also much chronic cough due to chronic bronchitis (sometimes
called 'Chronic Obstructive Pulmonary Disease' or other names). This is mostly due to tobacco
smoking, has a distinct tendency to slow progress. Firstly it is hacking-cough but step by step it
becomes moist coughing with pus expectoration. Duration of this process may be more than 3
months and coughing is followed increasing dyspnea.
You may notice that respiratory symptoms in advanced cases with disseminated tuberculosis
are more pronounced than in the cases with small forms of the disease: cough, sputum, blood-
spitting, chest wall pain, breathlessness, localized wheeze, frequent colds. Cough and breathlessness
are predominant. In advanced cases pus cough is often. General symptoms are: loss of weight, fever
and sweating, tiredness, loss of appetite. They are most important. Testing for disseminated
tuberculosis is conducted in a similar manner as for other forms of tuberculosis, although a number
of tests must be conducted on a patient to confirm diagnosis. Tests include chest x-ray, sputum
culture, bronchoscopy, open lung biopsy, blood cultures, fundoscopy, and electrocardiography. The
tuberculosis blood test, also called an Interferon Gamma Release Assay or IGRA, is a way to
diagnose latent TB. A variety of neurological complications have been noted in disseminated
tuberculosis patients—tuberculous meningitis and cerebral tuberculomas being the most frequent.
However, a majority of patients improve following antituberculous treatment. Rarely lymphangitic
spread of lung cancer could mimic diffuse pattern of tuberculosis on regular chest X-ray. The
tuberculin skin test, commonly used for detection of other forms of tuberculosis, is not useful in the
detection of disseminated tuberculosis. The tuberculin skin test fails due to the high numbers of
false positives. These false positives may occur because of higher rates of tuberculin anergy
compared to other forms of tuberculosis.
We must say about so general symptoms of illness: loss of weight, loss of appetite, tiredness
or fever The most reliable way of making the diagnosis is to find ТВ in a direct smear of the
sputum. Examination is by the Ziehl-Neelsen (ZN) staining method or, in well-equipped centres, by
using modem fluoroscopy with ultraviolet light, PCR and BACTEK.
There is nothing in the sputum which itself suggests tuberculosis: it may be mucoid,
purulent or contain blood. In tuberculosis, blood in the sputum may vary from a few spots to a
sudden coughing of a large amount of blood. Occasionally this blood loss is so great that the patient
quickly dies, usually from asphyxia due to aspirated blood. If you see blood in the sputum you must
always examine the sputum for ТВ.
Pain in the chest is not uncommon in disseminated tuberculosis. Sometimes it is just a dull
ache. Sometimes it is worse on breathing in (due to pleurisy). Sometimes it is due to muscle strain
from coughing. Sometimes the cough has been so severe that the patient has cracked a rib (cough
fracture). Breathlessness in tuberculosis is due to extensive disease in the lungs, or to pleural
effusion complicating the lung tuberculosis. The breathless patient frequently appears ill and has
lost weight. He will often have fever. Occasionally the patient has a localized wheeze. This is due
to local tuberculous bronchitis or to pressure of a lymph node on a bronchus. Sometimes the patient
seems to have other pulmonary diseases of not tuberculosis nature. So you should interpret all
evidence at the aspect of differential diagnosis of disseminated tuberculosis and alike diseases.
4.5. We pay attention practical doctors on such peculiarities of disseminated tuberculosis as:
1)Absence of clinical or laboratory manifestations pointing to different systemic diseases of not
tubercular nature, (for example enlargement of peripheral lymph nodes, presence of tumor in the
body, high febrile temperature etc.).
2) TMB isolation (they should be sought carefully with all modern techniques).
3) Tuberculosis cavity in the lung (which may be detected with the help of CT).
4) Presence of upper-lobe location of dissemination in combine with other signs of tuberculosis
(foci multiformity, lymphangitis, sclerosis changes etc.)
Physical signs. Often these do not help much. But do examine the patient carefully. You may find
useful signs:
General condition. Sometimes this may be good, in spite of advanced disease. But the patient may
be obviously ill. He may be very thin, with obvious loss of weight. He may be pale or have a flush
due to fever.
Fever. This can be of any type. There may be only slight rise of temperature in the evening. The
temperature may be high or irregular. Often there is no fever. Tuberculosis continues to be a
common disease in our region and one of its unusual presentation is fever of undetermined origin
(FUO).From 68 cases of FUO, the majority of the cases (44%), followed by neoplasm (19%),
collagen vascular disease (15%), miscellaneous (9%) and undiagnosed (13%). Tuberculosis (ТВ)
turned out to be the most common cause of fever of undetermined origin in this study (16.2%) and
it comprised 37% of patients in the infectious group. The majority of the patients had
extrapulmonary tuberculosis (9 out of 11). As we expected tuberculosis is an important cause of
FUO in our region where tuberculosis is still endemic. This is also true in other countries where the
incidence of this disease has declined significantly in recent decades.
Pulse is usually raised in proportion to fever.
Finger clubbing. You may find this, especially in a patient with extensive disease. Remember that
clubbing is common with lung cancer.
Chest. Often there are abnormal signs. There may be dullness to percussion or even bronchial
breathing in the upper part of both lungs. Occasionally there is a localized wheeze due to local
tuberculous bronchitis or pressure by a lymph node on a bronchus. In chronic tuberculosis, with
much fibrosis (scarring) the scarring may pull the trachea or the heart over to one side. At any stage
the physical signs of pleural effusion may be present. But some tines you will find nothing
abnormal in the chest.
The commonest is fine crepitations (crackles) in the interscapular part of one or both lungs. These
are heard particularly on taking a deep breath after coughing. Bubbling rales are the additional
breathing sounds that may appear thanks to a fluid accumulation in anatomical airway. Exudation,
transudate, bronchial secretion and blood may be in the capacity of this fluid. The fluid are stored
up in different pulmonary cavities are communicated both with respiratory and conducting airways.
During inhalation an air comes through this fluid and makes foam it resulting bubbles that are
bursting and may be registered as moist rales. Bubbly sounds are commonly recognized
predominantly during inspiration because not only of a violent current of air but thanks to a low
end-expiratory pressure in cavity. But sometimes moist rales may be detected during expiration.
They make out small bubbling rales; medium bubbling rales: large bubbling rales. These
characteristics depend on bronchi caliber. For instance small bubbling rales are generated in alveoli,
terminal bronchioles and little bronchi. Sometimes so called ringing rales may be heard. They-occur
in resonant cavity having smooth wall, in consolidation portions of the lung and near the stomach
gas bubble. At the same time the rales may be of different frequency and so are divided on the
fine rales with frequency 180-355 Hz (cycles per second) and the sonorous rales with frequency
710-1440 Hz (cycles per second). Dry rales are raised solely in bronchi as a result of any
adequate airway disturbance. Their origins are varied:
1) a viscid sputum small lingula on the large or medium bronchi wall oscillantion;
2) thread-like phlegm cross-pieces in the bronchial clear space vibration;
3) poor patient airway (by sputum small lump, mucous oedema, inside or outside swell) leading to
an air jet turbulence;
4) bronchiole wall trembling with bronchospasm.
Bronchiarctia as a common reason of dry rales results their birth during expiration when
ronchi are declining to arctation. Suggested above problems in large and medium bronchi result
buzzing or humming rales may be born. Whistling rales may be borne by small bronchi and
bronchioles.
X-ray (radiological) examination. You cannot diagnose tuberculosis with certainly on an X-ray.
Other diseases often look very similar. A normal chest X-ray for practical purposes excludes
tuberculosis. (Though very rarely tuberculosis causes tuberculous bronchitis which you cannot see
on an X-ray.) The X-ray shadows which strongly suggest tuberculosis are:
a) upper zone patch shadows (on both sides),
b) cavitation (particularly if more than one cavity)
c) calcified shadows may cause difficulties in diagnosis. Remember this may not be completely
diagnostic. Pneumonia and lung tumors can occur in areas of previous healed and calcified
tuberculosis. Some benign tumors contain calcification.
Other shadows which may be due to tuberculosis are:
a) oval or round solitary shadow (tuberculoma);
b) hilar and mediastinal shadows due to enlarged lymph nodes;
c) diffuse small nodular shadows (chronic miliary tuberculosis).
The correct reading of chest X-rays needs a lot of experience. If you suspect tuberculosis from the
X-ray and the sputum is negative, give a non-tuberculosis antibiotic (e.g. ampicillin, oxytetracyline)
for 7-10 days and repeat the X-ray. Shadows of an acute pneumonia will show improvement. But
beware of shadows which look smaller after 10 days but are in fact due to collapse of part of the
lung due to obstruction of a bronchus. It is a major error to diagnose tuberculosis on x-ray and
fail to examine the sputum.
Tuberculin test. Although, with proper attention to careful technique, tuberculin, testing is very
useful in measuring the prevalence of tuberculosis in a community, in many poorer countries it is
much less valuable as a tool for diagnosis. This is because the test may be negative due to
malnutrition or other diseases even though the patient has active tuberculosis. A strongly positive
test is, of course, a point in favor of tuberculosis, but a negative test does not exclude tuberculosis.
(Remember a strongly positive test is only a point in favor: many people without active
ttuberculosis have positive tests). There are two other problems in using the tuberculin test:
1) In many countries infection by other, often non-pathogenic, mycobacteria can result in a positive
tuberculin test, but usually a weak positive.
2) Problems of improper storage, improper dilution, absorption of tuberculin on to glass,
contamination etc. may make the test unreliable in your area. We suggest you consult a local
tuberculosis specialist who should be able to tell you whether the test will be valuable in your area.
3) Negative tuberculin test may be rather often because depression of immunity.
But in any case remember that, if other evidence suggests the diagnosis of tuberculosis, a negative
test does not exclude tuberculosis.
On the other hand a positive test, even a strongly positive test, only shows that the patient has
previously been infected. It does not prove that he has active tuberculous disease. It is merely a
point in favor. A positive test is particularly valuable in a young child at an age when fewer children
in the community will normally have positive tests.
Blood examination. Feebly marked anaemia is often caused by chronic disseminated pulmonary
tuberculosis. But anaemia is more likely to be due to other causes e.g. worms or malnutrition. The
white blood count is usually normal or low normal. (It is often raised in pneumonia.)
A raised erythrocyte sedimentation rate (ESR) may occur. But a normal result does not exclude
disseminated tuberculosis. It is therefore not a useful test and not worth doing.
4.5. Distinguishing tuberculosis from other conditions. The main conditions which have to be
distinguished are:
Pneumonia . In acute multi segmental focal pneumonia the symptoms usually come on suddenly. In
the X-ray the soft shadows may look like tuberculosis. This is especially so if they are in the upper
part of the lung. If the sputum is negative, give a non-tuberculous antibiotic for 7 days and X-ray
again. A raised white blood count is in favor of pneumonia. If you have no X-ray, a rapid fall of
temperature when you give the antibiotic makes the diagnosis likely to be pneumonia. Pneumonia
due to Pneumocystis carinii is a common complication of AIDS. There is often a low-grade fever
for several weeks and cough without sputum. The patient often becomes steadily more breathless.
You may find nothing abnormal when you examine the chest. X-ray of the chest may be normal but
may show diffuse shadowing. The picture may be like tuberculosis. But a patient with pulmonary
tuberculosis usually has sputum. If so, examine it for ТВ. If negative look for the cysts of
pneumocystis. If there is no sputum, do a bronchial lavage and look for the cysts (if this procedure
is possible in your hospital).
Lung cancer. In the X-ray a tumor may sometimes show a lot of metastases. Or infection
beyond a bronchus blocked by a tumor may cause a lung abscess with a cavity. If the sputum is
negative diagnosis may have to be made by bronchoscopy. A patient with lung cancer is almost
always a smoker. Feel also for an enlarged lymph node behind the inner end of the clavicle, a
common place for secondary tumor.
Lung staphylococcus disintegration. There is usually a lot of purulent sputum. The patient is
usually feverish and ill. If the purulent sputum is repeatedly negative for ТВ plural lung abscesses is
more likely. The white blood count is usually high. There is usually a lot of purulent sputum. It has
often been produced since childhood. Persistent moist coarse 'crackles' .
Bronchiectasis. Lung Tuberculosis in Adults may be repeatedly heard over the same area of
the lung. Sputum is negative for ТВ.
Asthma. Wheeze is not common in tuberculosis. But it may occasionally occur:
a) from enlarged lymph nodes, which may obstruct a bronchus or even the trachea,
b) from tuberculous bronchitis.
Either of these may cause a localized wheeze. Remember also that a few patients with severe
asthma may be on long-term corticosteroid drugs (such as prednisolone). This can weaken the
patient's defences against ТВ. He can then develop tuberculosis as well as asthma. If an asthma
patient develops a cough while under treatment/ or if he begins to run a fever or loses weight, test
his sputum for ТВ.
Pneumoconiosis is defined as a non-neoplastic lung reaction to inhalation of mineral or organic
dusts encountered in the workplace or environment. The majority of reactions are chronic, due to
exposure to dust over a period of many years and having latencies often exceeding several decades.
Lung fibrosis may have many causes and also may be host-dependent. Pneumoconiosis is one of the
causes of lung fibrosis, and it is important to distinguish it from other fibrotic and granulomatous
lung diseases which have different etiologies and treatments. Clinical manifestations: 1) Chronic
cough and shortness of breath on exertion may be reported, however usually due to industrial
bronchitis or smoking; 2) Mild loss of lung function; 3) Tightness in the chest; 4) Dyspnea;
5)Chronic cough with black sputum; 6) Pulmonary dysfunction (i. e. pulmonary hypertension); 7)
Right- sided heart failure due to lung dysfunction; 9) Cyanosis. Other constitutional symptoms such
as fever and night sweats may occur if a superimposed mycobacterial infection is present
Diagnosis and monitoring. If an individual presents any of the aforementioned symptoms, a series
of diagnosis methods are to be employed: 1) A full and detailed medical, occupational and
environmental history; 2)Physical examination with a focus on the chest area; 3) Use of pulmonary
function tests (PFTs) (i.e Spirometry) in order to determine the severity of the impairment of lung
function. Individuals suffering from simple CWP show no significant loss of lung capacity and
function. However, the alveolar-arterial pressure gradient can show a minor decrease, while the
diffusing capacity (P category – according to the ILO system to be described further) is slightly
reduced. Also, secondary to physiological shunting, minimal hypoxemia can be observed. A slight
increase in residual volume and in compliance of the lung can result if focal emphysema is present.
In addition, pulmonary hypertension can occur if the size of the conglomerate mass is significantly
large to destroy vascularity. Measurement of arterial blood gases (ABGs) can be used to the
determine impairments between oxygen and carbon dioxide in the alveoli. CBC count and a
sputum culture can be performed, if needed, to eliminate the possibility of other infective processes
The 6-minute walk test (6MWT), a simple, additional test that can be performed as a mean of
quantifying possible lung impairment due to CWP. Imaging procedures , such as chest X-rays and
Computed Tomography (CT) scans, remain the primary diagnostic tools used to visualize the
nodules and lung scarring and to evaluate the presence and progression of the disease. The
radiographs obtained are to be compared against the standardized set of X-rays developed by the
International Labor Organization (ILO) which reflects the amount of retained coal in the lungs. This
12 point classification scale represents a continuum of dust accumulation with nodule formation
from category 0/0 to 3/4. Bronchoscopy with a lung biopsy, an invasive technique that involves the
removal of a small piece of lung tissue to be examined in the laboratory. Of note, Reichert and
Bensadoun (2009) conducted a small study which proved that positron emission tomography (PET)
method is off limited value in the evaluation of CWP, as it yields a high false-positive rate
Therefore, the differential diagnosis of CWP should be done in relation to ILO Classification Guide
System and a full occupational history. The other diseases for which Pneumoconiosis is listed as a
possible alternative diagnosis in their lists include: histoplasmosis, idiopathic, pulmonary fibrosis,
sarcoidosis.
Sarcoidosis is an inflammatory disease that affects multiple organs in the body, but mostly the
lungs and lymph glands. In people with sarcoidosis, abnormal masses or nodules (called
granulomas) consisting of inflamed tissues form in certain organs of the body. These granulomas
may alter the normal structure and possibly the function of the affected organ(s).
Symptoms of Sarcoidosis. The symptoms of sarcoidosis can vary greatly, depending on which
organs are involved. Most patients initially complain of a persistent dry cough, fatigue, and
shortness of breath. Other symptoms may include:
1)Tender reddish bumps or patches on the skin. 2)Red and teary eyes or blurred vision. 3)Swollen
and painful joints. 4)Enlarged and tender lymph glands in the neck, armpits, and groin. 5)Enlarged
lymph glands in the chest and around the lungs. 6)Hoarse voice. 7) Pain in the hands, feet, or other
bony areas due to the formation of cysts (an abnormal sac-like growth) in bones. 8) Kidney stone
formation. 9) Enlarged liver. 10) Development of abnormal or missed heart beats (arrhythmias),
inflammation of the covering of the heart (pericarditis), or heart failure. 11) Nervous system effects,
including hearing loss, meningitis, seizures, or psychiatric disorders (for example, dementia,
depression, psychosis).
In some people, symptoms may begin suddenly and/or severely and subside in a short period of
time. Others may have no outward symptoms at all even though organs are affected. Still others
may have symptoms that appear slowly and subtly, but which last or recur over a long time span.
Sarcoidosis most often occurs between 20 and 40 years of age, with women being diagnosed more
frequently than men. The disease is 10 to 17 times more common in African-Americans than in
Caucasians. People of Scandinavian, German, Irish, or Puerto Rican origin are also more prone to
the disease. It is estimated that up to four in 10,000 people in the U.S. have sarcoidosis.
The exact cause of sarcoidosis is not known. It is a type of autoimmune disease associated with an
abnormal immune response, but what triggers this response is uncertain. How sarcoidosis spreads
from one part of the body to another is still being studied.
Diagnosis. There is no single way to diagnose sarcoidosis, since all the symptoms and laboratory
results can occur in other diseases. For this reason, doctor should carefully review a medical history
and examine a case to determine if she has sarcoidosis. The main tools may be used to diagnose
sarcoidosis include: 1) Chest X-rays to look for cloudiness (pulmonary infiltrates) or swollen lymph
nodes (lymphadenopathy). 2) CT scan to provide an even more detailed look at the lungs and lymph
nodes than provided by a chest X-ray. 3) Pulmonary function (breathing) tests to measure how well
the lungs are working. 4) Bronchoscopy to inspect the bronchial tubes and to extract a biopsy (a
small tissue sample) to look for granulomas and to obtain material to rule out infection.
Bronchoscopy involves passing a small tube (bronchoscope) down the trachea (windpipe) and into
the bronchial tubes (airways) of the lungs. In many people with sarcoidosis, the disease appears
briefly and then disappears without the person even knowing they have the disease. Twenty percent
to 30% of people have some permanent lung damage. For a small number of people, sarcoidosis is a
chronic condition. In some people, the disease may result in the deterioration of the affected organ.
Rarely, sarcoidosis can be fatal. Death usually is the result of complications with the lungs, heart, or
brain

4.6. Literature
1. Nunes H., Bouvry D, Soler P, and al. Sarcoidosis // Orphanet Journal of Rare Diseases. -
2007, №2. – P. 46-52.
2. Roy S. Herbst, M.D., Ph.D., John V. Heymach, M.D., Ph.D., and Scott M. Lippman, M.D.
Lung Cancer // N Engl J Med. - 2008; V. 359. – P.1367-1380.