Sarcoidosis of the lungs: diagnosis

The examination program for sarcoidosis of the respiratory system

1. Common blood tests, urine tests.
2. Biochemical blood test: determination of bilirubin, aminotransferase, alkaline phosphatase, total protein and protein fractions, seromucoid, sialic acids, haptoglobin, calcium, free and protein-bound hydroxyproline.
3. Immunological studies: determination of B and T-lymphocytes, subpopulations of T-lymphocytes, immunoglobulins, circulating immune complexes.
4. Investigation of bronchial lavage fluid: cytological analysis, determination of T-lymphocytes and their subpopulations, natural killers, immunoglobulins, activity of proteolytic enzymes and inhibitors of proteolysis.
5. X-ray examination of the lungs.
6. Spirography.
7. CT.
8. Bronchoscopy.
9. Biopsy and histological examination of lymph node biopsy specimens and pulmonary tissue obtained from transbronchial or open lung biopsy.

Laboratory data

General blood analysis. There are no specific changes. The hemoglobin content and the number of erythrocytes are usually normal. In patients with acute form of the disease there is an increase in ESR and leukocytosis, in the chronic form of the disease, there can be no significant changes. Erosinophilia is noted in 20% of patients, and absolute lymphopenia in 50%.

General analysis of urine - without significant changes.

Biochemical blood analysis - in the acute form of sarcoidosis, serumucoid, haptoglobin, sialic acid (biochemical markers of inflammation), gamma globulin levels may increase. In the chronic form of the disease, these parameters vary little. When involved in the pathological process of the liver, there may be an increase in the level of bilirubin and aminotransferase activity.

Approximately 15-20% of patients increased the calcium content in the blood. Characteristic is also the increase in blood levels of proteolytic enzymes and anti-proteolytic activity. In the active phase of the disease, an increase in the level of the common or protein-bound oxyproline can be detected, which is accompanied by increased urinary excretion of hydroxyproline, glycosaminoglycans, uroglycoproteins, which reflects the processes of fibro-formation in the lungs. In the chronic course of sarcoidosis, these parameters vary slightly.

In patients with sarcoidosis an increase in the content of angiotensin-converting enzyme was noted. This fact is important for the diagnosis of sarcoidosis, as well as determining its activity. Angiotensin-converting enzyme is produced by endothelial cells of pulmonary vessels, as well as epithelioid cells of sarcoid granulomas. In other diseases of the bronchopulmonary system (tuberculosis, bronchial asthma, chronic obstructive bronchitis, lung cancer ), the level of angiotensin-converting enzyme in serum is reduced. At the same time, the level of this enzyme is increased in diabetes mellitus, viral hepatitis, hyperthyroidism, silicosis, asbestosis, Gaucher disease.

In patients with sarcoidosis, there was also an increase in the content of lysozyme in the blood.

Immunological research. For the acute form of sarcoidosis and acute exacerbation of the chronic course, a decrease in the number of T-lymphocytes and their functional capacity is characteristic, as evidenced by the results of the reaction of the imperious transformation of lymphocytes with phytohemagglutinin. Characteristic is also a decrease in the content of T-lymphocyte-helpers and, accordingly, a decrease in the T-helper / T suppressor index.

In patients with stage I sarcoidosis, the activity of natural killers is decreased, in the II and III stages in the exacerbation phase it is increased, in the phase of remission it is not significantly altered. In the active phase of the disease there is also a decrease in the phagocytic function of leukocytes. In many patients, an increase in the absolute number of B lymphocytes, as well as the level of IgA, IgG, and circulating immune complexes, mainly in the active phase (acute sarcoidosis and exacerbation of the chronic form) is noted. In some cases, anti-pulmonary antibodies are also found in the blood

Kweim test - used to diagnose sarcoidosis. Standard sarcoid antigen is injected intradermally into the forearm area (0.15-0.2 ml) and after 3-4 weeks (the time of granuloma formation) the site of antigen administration is excised (skin together with subcutaneous fatty tissue) even in the absence of visible changes. The biopsy is examined histologically. A positive reaction is characterized by the development of a typical sarcoid granuloma. Erythema, which occurs 3-4 days after the administration of the antigen, is not taken into account. The diagnostic information content of the sample is about 60-70%.

Clinical examination of sputum - no significant changes are usually detected.

Investigation of bronchial lavage fluid. A study of fluid obtained by washing the bronchi (bronchial lavage fluid) is given a great diagnostic value. The following changes are typical:

• cytological examination of bronchial lavage fluid - an increase in the total number of cells, an increase in the percentage of lymphocytes, these changes are particularly pronounced in the active phase of the disease and less noticeable in the phase of remission. As the progression of sarcoidosis and the increase in fibrosis processes in the bronchial lavage fluid, the content of neutrophils increases. The content of alveolar macrophages in the active phase of the disease is reduced, as the active process subsides, it rises. It should not be overestimated, of course, the significance of cytological examination of bronchial lavage fluid or eudopulmonary cytogram, since the increased content of lymphocytes in it is also noted in many patients with adipathic fibrosing alveolitis, diffuse connective tissue diseases with pulmonary parenchyma involvement, lung cancer and AIDS;
• Immunological study - increased IgA and IgM content in the active phase of the disease; increased the number of T-helpers, reduced the level of T-suppressors, significantly increased the coefficient of T-help / T-suppressors (as opposed to changes in peripheral blood); sharply increased the activity of natural killers. These immunological changes in the lavage fluid of the bronchi are much less pronounced in the phase of remission;
• biochemical study - increased activity of angiotensin-converting enzyme, proteolytic enzymes (including elastases) and a decrease in anti-proteolytic activity.

Instrumental research

X-ray examination of the lungs. This method is of great importance in the diagnosis of sarcoidosis, especially when it comes to forms of the disease that do not show a clear clinical symptomatology. As indicated above, based on the data of the X-ray study, Wurm even identifies the stages of sarcoidosis.

The main radiographic manifestations of lung sarcoidosis are the following:

• an increase in the intrathoracic lymph nodes (mediastinal lymphadenopathy) is observed in 80-95% of patients and is essentially the first radiologic symptom of sarcoidosis (stage I of sarcoidosis of the lung according to Wurm). An increase in the intrathoracic (bronchopulmonary) lymph nodes is usually bilateral (sometimes one-sided at the onset of the disease). By increasing the intrathoracic lymph nodes, the roots of the lungs increase and expand. The enlarged lymph nodes have clear polycyclic outlines and a homogeneous structure. A stepped contour of the image of the lymph nodes is very characteristic due to the imposition of shadows in the anterior and posterior groups of bronchopulmonary lymph nodes.

It is also possible to expand the median shade in the mediastinum region by simultaneously increasing paratracheal and tracheobronchial lymph nodes. Approximately 1 / 3-1 / 4 patients in the enlarged lymph nodes show calcifications - calcifications of various forms. Calcinates are usually detected during a prolonged course of the primary chronic form of sarcoidosis. In some cases, enlarged hilar lymph nodes squeeze nearby bronchi, which leads to the appearance of areas of hypoventilation and even atelectasis of the lungs (a rare symptom).

These changes from the side of the intrathoracic lymph nodes are better detected by computed tomography of the lungs or X-ray tomography.

As indicated, with sarcoidosis, spontaneous or under the influence of treatment regression of the disease; in this case, the lymph nodes are significantly reduced, the polycyclicity of their contours disappears and they do not look like conglomerates;

• X-ray changes in the lungs depend on the duration of the course of sarcoidosis. In the early stages of the disease enrichment of the pulmonary picture is noted due to peribronchial and perivascular network and shadows (II stage according to Wurm). Further focal shadows of various round shape appear, bilateral, scattered throughout all pulmonary fields (IIB-IIB-IIG stage according to Wurm, depending on the size of the foci).

The centers are located symmetrically, mainly in the lower and middle parts of the lungs. Characterized by a more pronounced lesion of the root zones than the peripheral parts.

With resorption of the foci, the pulmonary pattern is gradually normalized. However, with the progression of the process, there is an intensive proliferation of connective tissue - diffuse pneumosclerotic changes ("honeycomb lung") (stage III by Wurm). In some patients, large spillage formations can be observed. Possible atypical radiographic changes in the lungs in the form of infiltrative changes. Probably also the defeat of the pleura with the accumulation of fluid in the pleural cavities.

Radioisotope scanning of the lungs. This method is based on the ability of granulomatous foci to accumulate the 67Ga citrate isotope. The isotope accumulates in the lymph nodes (intrathoracic, cervical, submaxillary, if they are affected), pulmonary foci, liver, spleen and other affected organs.

Bronchoscopy. Changes in the bronchi are observed in all patients with acute form of sarcoidosis and exacerbation of the chronic form of the disease. Characteristic changes in the vessels of the bronchial mucosa (enlargement, thickening, tortuosity), as well as tuberous eruptions (sarcoid granulomas) in the form of plaques of various sizes (from millet grains to pea). At the stage of fibrosis formed granulomas on the bronchial mucosa are visible ischemic spots - pale areas lacking blood vessels.

Examination of the function of external respiration. In patients with stage I sarcoidosis, there are no significant disturbances in the function of external respiration. With the progression of the pathological process, a moderately pronounced restrictive syndrome develops, characterized by a decrease in LEL, a moderate decrease in the diffusivity of the lungs, and a decrease in the partial pressure of oxygen in the arterial blood. At the expressed defeat of lungs at far gone pathological process disturbances of a bronchial patency can be observed (approximately at 10-15% of patients).

Histological examination of biopsies of affected organs. Histological examination of biopsies allows verifying the diagnosis of sarcoidosis. First of all, the biopsy is made from the most accessible places - the affected areas of the skin, enlarged peripheral lymph nodes. It is also desirable to biopsy the bronchial mucosa if bronchoscopy reveals sarcoid tubercles. In some cases, transbronchial biopsy of lymph nodes and lung tissue may be effective. With an isolated increase in the intrathoracic lymph nodes mediastinoscopy with appropriate lymph node biopsy or parasternal mediastinotomy is performed.

If the results of transbronchial lung biopsy were negative and at the same time there are x-ray signs of bilateral focal changes in the lung tissue in the absence of intrathoracic lymphadenopathy (a rare situation), an open lung biopsy is performed. If the liver is severely affected, it is biopsy under laparoscopic control, and less often a biopsy of the salivary glands.

The diagnostic criterion of sarcoidosis is the detection in tissue biopsies of epithelial cell granulomas without necrosis (for a detailed description of granuloma see "Pathogenesis and pathomorphology of sarcoidosis").

Thoracoscopy - is performed when there are signs of pleural involvement in the pathological process. On the pleural surface, whitish-yellowish sarcoid granulomas are visible, which also undergo biopsy.

ECG changes are observed with the involvement of the heart in the pathological process and are characterized by extrasystolic arrhythmia, rarely - atrial fibrillation, atrioventricular and intraventricular conduction abnormalities, a decrease in the amplitude of the T wave, mainly in the left thoracic leads. In the primary chronic course and the development of severe respiratory failure, the electric axis of the heart can be deflected to the right, the appearance of signs of increased stress on the myocardium of the right atrium (high pointed teeth P).

Ultrasound examination of the heart - when involved in the pathological process of the myocardium reveals dilatation of the heart cavities, a decrease in the contractility of the myocardium.

Determination of the activity of the pathological process

Determination of the activity of sarcoidosis is of great clinical importance, since it allows to decide the need for the appointment of glucocorticoid therapy.

According to the conference in Los Angeles (USA, 1993) the most informative tests that allow to determine the activity of the pathological process in sarcoidosis are:

• clinical course of the disease (fever, polyarthralgia, polyarthritis, skin changes, erythema nodosum, uveitis, splenomegaly, increased dyspnoea and cough);
• negative dynamics of the radiographic picture of the lungs;
• deterioration of ventilation capacity of the lungs;
• increased activity of angiotensin-converting enzyme in blood serum;
• change in the ratio of cell populations and the ratio of T-helpers / T-suppressors.

Of course, one should take into account the increase in ESR, the high level of circulating immune complexes, the "biochemical inflammatory syndrome", but all these indicators are given less importance.

Differential diagnosis of respiratory sarcoidosis

Lymphogranulomatosis

Lymphogranulomatosis (Hodgkin's disease) is a primary malignant neoplasm of the lymphatic system, characterized by its granulomatous structure with the presence of giant Berezovsky-Sternberg cells, which proceeds with the involvement of lymph nodes and internal organs.

Differential diagnosis of sarcoidosis and lymphogranulomatosis is extremely important from the point of view of treatment and prognosis.

Lymphosarcoma

Lymphosarcoma is a malignant extramednostic tumor from lymphoblasts (or lymphoblasts and prolymphocytes). The disease is more common in men over the age of 50 years. The primary focus (the organ from which the tumor clan originates) is the lymph nodes of the neck (usually one-sided lesion), less often the other groups of lymph nodes. In some cases, the primary localization of the tumor in the mediastinal lymph nodes is indicated. Affected lymph nodes (neck, mediastinum) makes it differentiate sarcoidosis with this disease.

The specific features of lymph node involvement in lymphosarcoma are the following:

• preservation of normal properties of enlarged lymph nodes at the very beginning of the disease (lymph nodes are mobile, painless, dense-elastic);
• rapid growth, consolidation and formation of conglomerates in the future;
• fusion of lymph nodes with surrounding tissues, disappearance of mobility with their further growth.

These features are not characteristic of sarcoidosis.

With mesenteric or gastrointestinal lymphosarcoma localization, it is almost always possible to detect a tumor-like formation in the abdominal cavity when palpation, with abdominal pain, nausea, vomiting, often bleeding, and symptoms of intestinal obstruction.

In the late stage of lymphosarcoma, generalized lymph node enlargement is possible, lung damage is observed, which is manifested by coughing, shortness of breath, hemoptysis. In a number of cases, exudative pleurisy, renal involvement with hematuria develops, the liver is enlarged

Lymphosarcoma is accompanied by fever, pouring sweat, weight loss. There is never a spontaneous recovery or at least a reduction in the symptoms of the disease.

Such a course of the disease for sarcoidosis is not typical, but it should be remembered that in sarcoidosis it is possible in rare cases to defeat mesenteric or even retroperitoneal lymph nodes.

The final diagnosis of lymphosarcoma is established with the help of lymph node biopsy. Tumor cells are identical to cells of acute lymphoblastic leukemia (lymphoblasts).

Briel-Simmers disease

Bril-Simmers disease - non-Hodgkin's lymphoma of B-cell origin, is more common in middle-aged and older men. During the disease, two stages are distinguished: benign (early) - lasts 4-6 years, and malignant - lasts about 1-2 years. In the early stage there is an increase in the lymph nodes of any one group, most often the cervical, less often - axillary, inguinal. The enlarged lymph nodes are painless, not soldered to each other, to the skin, they are mobile.

In the second (malignant) stage, the clinical picture is identical to that of generalized lymphosarcoma. Characteristic is also the development of compression syndrome (with lesion of mediastinal lymph nodes) or ascites (with lesion of mesenteric lymph nodes).

The diagnosis of the disease is verified using a lymph node biopsy. In the early stage, a characteristic feature is a sharp increase in follicles (macrofollicular lymphoma). In the malignant stage with a biopsy of the lymph nodes, a picture is found that is characteristic of lymphosarcoma.

Cancer metastases in peripheral lymph nodes

In malignant tumors, it is possible to metasgas and increase the same groups of lymph nodes as in sarcoidosis. In the cervical lymph nodes most commonly metastasize the cancer of the thyroid gland, larynx; in supraclavicular - cancer of the breast, thyroid, stomach (left-sided metastasis of Vikhrova); in axillary - breast cancer and lung cancer; In the inguinal - tumors of the urino-genital organs.

The nature of the increase in lymph nodes is refined quite easily - the clinical signs of the primary tumor, as well as the results of biopsy of enlarged lymph nodes, are taken into account. In the biopsy, atypical cells are determined and often cells that are characteristic of a particular tumor (for example, in hypernum, thyroid cancer).

Lung cancer

Differentiate sarcoidosis with lung cancer usually in the first and second stages of sarcoidosis.

Acute leukemia

In acute leukemia, along with an increase in peripheral lymph nodes, an increase in the intrathoracic lymph nodes is possible, which leads to differential diagnosis between acute lymphoblastic leukemia and sarcoidosis. Differential diagnosis between these diseases is simple. For acute leukemia characterized by a severe, progressive course without spontaneous remissions, fever, severe sweating, severe intoxication, anemia, thrombocytopenia, hemorrhagic syndrome. The appearance of imperious cells in the peripheral blood, leukemia "failure" (the leukocyte formula determines the youngest and mature cells, the number of intermediate forms is sharply reduced or they are absent altogether). Of decisive importance in the diagnosis of acute leukemia is, of course, sternal puncture. In the myelogram, a large number of blasts are detected (more than 30%).

Tuberculosis

It is often necessary to conduct differential diagnosis of sarcoidosis and pulmonary forms of tuberculosis.

Lymph node involvement in sarcoidosis should also be differentiated from tuberculosis of peripheral lymph nodes.

The defeat of lymph nodes in tuberculosis can be local (increased mainly cervical, less often - underarm, very rarely - inguinal lymph nodes) or generalized (involving at least three groups of lymph nodes in the pathological process).

Tuberculosis of peripheral lymph nodes has the following characteristic features:

• long, wavy current;
• mild or moderately dense consistency of lymph nodes, their small mobility (in connection with the development of the inflammatory process);
• absence of soreness on palpation;
• caseous melting of lymph nodes; with the skin over the node hyperemic, thinning, there is a fluctuation, then there is a breakthrough of the contents, a fistula is formed. In the subsequent healing of the fistula occurs with the formation of a skin scar;
• reduction and significant consolidation of affected lymph nodes (they resemble pebbles) after remission of the caseous process in them;
• the possibility of recurrence of tuberculous lesions and caseous decay;
• detection in the fistula of mycobacterium tuberculosis.

These features of lymph node involvement in tuberculosis are not at all characteristic of sarcoidosis. In difficult cases for diagnosis, it is necessary to make a biopsy of the affected lymph node with subsequent histological examination. Tuberculosis lymphadenitis is also characterized by a positive tuberculin test.

Chronic lymphatic leukemia

With chronic lymphocytic leukemia, marked peripheral lymphadenopathy develops, and therefore it is necessary to differentiate chronic lymphocytic leukemia with sarcodosis.

Chronic lymphocytic leukemia is characterized by the following features:

• enlarged lymph nodes (mainly cervical and axillary) reach significant dimensions, are painless, not soldered to each other and to the skin, they do not ulcerate and do not get inflamed;
• the spleen and liver are enlarged;
• the number of leukocytes in the peripheral blood is progressively increasing, reaching high values (50-100 x 10 ⁹ / li), with absolute lymphocytosis (75-90% of lymphocytes in the leukocyte formula) with a predominance of mature cells;
• in the blood smear Botkin-Humprecht cells - lymphocytes destroyed during the preparation of the smear are determined.

Usually, these signs make it possible to diagnose chronic lymphocytic leukemia. If there is any doubt about the diagnosis, a peripheral lymph node biopsy can be performed. The pathomorphological substrate of chronic leukemia is predominantly mature lymphocytes, but there are also lymphoblasts and prolymphocytes.

Lymphocyte

Lymphocytoma is a well-differentiated lymphocytic tumor. Primary localization of the tumor is extraosternal, in peripheral lymph nodes, spleen, less often in the stomach, lungs, skin. If the primary localization of the tumor clone is peripheral lymph nodes, the increase in cervical or axillary lymph nodes is more often noted. However, in the future, the generalization of the pathological process inevitably takes place, which consists in an increase in other groups of peripheral lymph nodes and spleen. This stage is characterized by a significant increase in lymphocytes in the peripheral blood. At this stage it is not difficult to distinguish lymphocytes from sarcoidosis. In difficult cases, a peripheral lymph node biopsy can be performed and thus differentiate the two diseases. It should be noted that with a significant spread of the process, it is difficult to distinguish the lymphocyte from chronic lymphocytic leukemia.

Infectious mononucleosis

Infectious mononucleosis is always accompanied by an increase in peripheral lymph nodes, so it is necessary to differentiate this disease and sarcoidosis.

Differentiating infectious mononucleosis can be based on the following characteristic symptoms:

• an increase in the supineum and occipital lymph nodes, they are of a dense elastic consistency, moderately painful, not soldered to surrounding tissues, not opened, do not form fistulas;
• spontaneous reduction in the size of enlarged lymph nodes by the 10-14 day of the disease;
• presence of fever, hepatosplenomegaly;
• detection of peripheral blood leukocytosis, lymphocytosis, monocytosis and a characteristic feature - atypical mononuclear cells (lymphomonocytes);
• Positive serologic response of Paul-Bunnel, positive test of Lovrik-Volner (agglutination of erythrocytes of sheep treated with papain), Goff-Bauer (agglutination of horse erythrocytes).

Infectious lymphocytosis

Infectious lymphocytosis is a disease of the viral etiology, characterized by lymphocytosis. There may be an increase in the cervical lymph nodes.

The characteristic features of infectious lymphocytosis are:

• a moderate increase in the cervical lymph nodes and very rarely others;
• subfebrile body temperature, weakness, rhinitis, conjunctivitis, dyspeptic phenomena, abdominal pain;
• pronounced leukocytosis (30-100 x 10 ⁹ / l), a significant predominance in the leukocyte formula of lymphocytes - 60-90% of all cells;
• benign course - rapid onset of recovery, disappearance of clinical signs of the disease, complete normalization of the picture of peripheral blood.

Examples of the formulation of the diagnosis

1. Sarcoidosis of the lungs, stage I, remission phase, DNI.
2. Sarcoidosis of the lungs, stage II, exacerbation phase, DNI. Sarcoidosis of the skin of the posterior surface of both forearms. Nodular erythema in the region of both shins.

[1], [2], [3], [4], [5], [6]