Idiopathic hemosiderosis of the lungs

Idiopathic hemosiderosis of the lungs is a disease of the lungs, characterized by repeated hemorrhages to the alveoli and a wave-like recurrent course, hypochromic anemia and a wave-like recurrent course.

The etiology and pathogenesis of the disease have not been adequately studied. Congenital inferiority of elastic fibers of small and medium vessels of the lung is assumed, which leads to their expansion, blood stasis and penetration of red blood cells through the vessel wall. Most researchers consider hemosiderosis lungs as an immunoallergic disease. In response to a sensitizing agent, autoantibodies are formed, an antigen-antibody reaction is developed, the shock organ for which are the lungs, which leads to the expansion of capillaries, stasis and diapedesis of erythrocytes into the lung tissue with deposition of hemosiderin.

[1], [2], [3],

Epidemiology

The disease occurs mainly in children and young people.

[4], [5], [6], [7], [8], [9], [10]

Causes of the idiopathic hemosiderosis of the lungs

The reason is unknown. The congenital inferiority of the elastic fibers of the vessels of the small circulation, especially the microcirculatory bed, is supposed to lead to dilatation of the pulmonary capillaries, marked slowing of the blood flow, diapedesis of erythrocytes into the alveoli, pulmonary parenchyma and subsequent deposition of hemosiderin. There is a point of view about the possible role of congenital anomalies of vascular anastomoses between the bronchial arteries and pulmonary veins.

However, recently the theory of the immunocomplex origin of the disease has become most widespread. It is possible the formation of antibodies to the components of the wall of the vessels of the lungs, followed by the formation of antigen-antibody complexes primarily in the microcirculatory bed of the lungs, which leads to necrosis of the vascular wall with hemorrhages in the alveoli, lung parenchyma. The large role of the cytotoxic effect of immune lymphocytes on the vascular wall is also not excluded.

For idiopathic pulmonary hemosiderosis, the following geomorphological changes are characteristic:

• filling of alveoli with erythrocytes;
• detection in the alveoli, alveolar courses and respiratory bronchioles, as well as in the interstitial tissue of a large number of alveolar macrophages filled with hemosiderin particles;
• thickening of alveoli and interalveolar septa;
• development as the disease progresses diffuse pneumosclerosis, degenerative changes in the elastic tissue of the lung;
• disruption of the basal membrane structure of capillaries of interalveolar septa (according to electron microscopic data)

[11], [12], [13], [14], [15], [16], [17],

Symptoms of the idiopathic hemosiderosis of the lungs

Idiopathic pulmonary hemosiderosis can be acute or acquire a chronic course with repeated exacerbations. Acute flow is characteristic mainly for children.

Complaints of patients with acute course or exacerbation of the disease are quite typical. Patients are disturbed by a cough with separation of bloody sputum. Hemoptysis is one of the main symptoms of the disease and can be expressed significantly (pulmonary hemorrhage). Cases without hemoptysis are very rare. In addition, patients complain of shortness of breath (especially with exercise), dizziness, tinnitus, flies before the eyes. These complaints are due, mainly, the development of anemia due to prolonged hemoptysis. In the origin of dyspnea, the development of diffuse pneumosclerosis in the progressing course of the disease is also important. Many patients have pain in the chest, joints, stomach, body temperature rises, perhaps significant weight loss.

At the onset of remission, the patients' well-being is significantly improved and they can not make complaints at all or complaints can be expressed slightly. The duration of remission varies, but after each exacerbation, as a rule, decreases.

[18], [19]

Diagnostics of the idiopathic hemosiderosis of the lungs

When examining patients, attention is drawn to the pallor of the skin and visible mucous membranes, icteric sclera, cyanosis. Severity of pallor depends on the degree of anemia, cyanosis - on the degree of respiratory failure. With percussion of the lungs, dullness of percussion sound is determined (mainly in the lower parts of the lungs). With extensive hemorrhages in the lung tissue blunting of percussion sound is much more pronounced and bronchial breathing can be heard above the zone of blunt sound. Often such a patient, especially in acute or severe exacerbation of the disease, is diagnosed with bilateral pneumonia. With auscultation of the lungs, an important sign of idiopathic hemosiderosis of the lungs is determined - widespread crepitation can be heard by moist fine-bubbly, and also dry wheezing. With the development of bronchospastic syndrome, the number of dry wheezing (whistling and buzzing) increases sharply. With auscultation of the heart, attention is drawn to the muffledness of tones in the development of a chronic pulmonary heart, the accent of tone II on the pulmonary artery is determined, with the decompensation of the pulmonary heart, the liver is enlarged. Liver enlargement in 1/3 of patients is observed in the absence of decompensated pulmonary heart. Possible an increase in the spleen.

Idiopathic hemosiderosis of the lungs can be complicated by severe infarct-pneumonia (it can be extensive and accompanied by severe respiratory failure), recurrent pneumothorax, heavy bleeding. These complications can cause death.

Laboratory data

1. A general blood test is characteristic of hypochromic anemia. It is manifested by a decrease in the level of hemoglobin, the number of erythrocytes, color index, anisocytosis, poikilocytosis. Anemia can be markedly expressed. There is also reticulocytosis.

With severe exacerbation of hemosiderosis of the lungs, as well as with the development of infarct-pneumonia, pronounced leukocytosis appears, the shift of the leukocyte formula to the left, increases the ESR. In 10-15% of patients there is eosinophilia.

2. The general analysis of urine - without significant changes, but sometimes protein, erythrocytes is determined.
3. Biochemical analysis of blood - increases the content of bilirubin, alanine aminotransferase, alpha2- and gamma globulins, decreases the iron content, increases the total iron binding capacity of blood serum.
4. Immunological studies - no significant changes are detected. In some patients, it is possible to reduce the number of T-lymphocytes, increase immunoglobulins, the appearance of circulating immune complexes.
5. Sputum analysis. Erythrocytes and siderophages are detected - alveolar macrophages loaded with hemosiderin. Sputum analysis should be performed frequently, as a single study may not be informative.
6. Investigation of bronchial lavage fluid - siderophages are found in the bronchial washings.
7. Analysis of bone marrow puncture - myelogram is characterized by a decrease in the number of sideroblasts - red bone marrow cells containing iron lumps. There may be a sign of increased erythropoiesis-an increase in the number of normoblasts (probably as a manifestation of a compensatory reaction to the development of anemia).

[20],

Instrumental research

X-ray examination of the lungs. Radiologically it is possible to distinguish the following stages of the disease:

• Stage I - a decrease in the transparency of lung tissue (veil-like darkening of both lungs), which is caused by diffuse small hemorrhages in the lung tissue;
• II stage - manifested by the presence of multiple small foci of rounded shape from 1-2 mm to 1-2 cm in diameter scattered diffusely across all pulmonary fields. These foci gradually dissolve within 1-3 weeks. The appearance of new foci coincides with the phase of exacerbation of the disease;
• III stage - characterized by the appearance of extensive intense darkening, which is very similar to infiltrative shadows in pneumonia. The appearance of such intensive darkening is caused by the development of edema and inflammation around the foci of hemorrhage. A characteristic feature of this stage, like the second, is the rather rapid disappearance and re-emergence of infiltrates in other parts of the lungs in which a hemorrhage occurred;
• IV stage - intensive interstitial fibrosis is revealed, which develops due to repeated hemorrhages and the organization of fibrin in the alveoli.

These x-ray changes, as a rule, are bilateral, extremely rarely one-sided.

The increase in the intrathoracic lymph nodes is not characteristic, but can be observed in 10% of patients.

With the development of chronic pulmonary hypertension, the bulging of the cone of the pulmonary artery and an increase in the right heart are detected. With the development of pneumothorax, partial or complete collapse of the lung is determined.

Perfusion lung scintigraphy. For idiopathic hemosiderosis, marked bilateral disturbances of pulmonary blood flow are characteristic.

Investigation of the ventilation capacity of the lungs. With the progression of the disease, a restrictive respiratory failure develops, characterized by a decrease in LEL. It is often enough to determine the violation of bronchial patency, as evidenced by a decrease in the FEV1 index of the Tiffno index, the peak flow meter.

ECG. Progressing anemia leads to the development of myocardial dystrophy, which causes a decrease in the amplitude of the T wave in many leads, especially in the left thoracic. With significantly expressed myocardial dystrophy, it is possible to lower the ST interval downward from the isoline, the appearance of various types of arrhythmias (most often ventricular extrasystole). With the development of chronic pulmonary hypertension, there are signs of myocardial hypertrophy of the right atrium and right ventricle.

Investigation of the gas composition of blood. With the development of severe respiratory failure, arterial hypoxemia arises.

Histological examination of lung tissue biopsy specimens. A biopsy of the lung tissue (perebronchial, open lung biopsy) is very limited, only with the absolute impossibility of diagnosing the disease. Such a maximum narrowing of the indications for lung biopsy is associated with an increased risk of hemorrhage.

Histological examination of pulmonary tissue biopsy specimens in the alveoli reveals a large number of hemosiderophages, as well as severe fibrosis of interstitial tissue.

Ultrasound examination of the abdominal cavity organs. With prolonged existence of the disease, an increase in the liver and spleen is often observed.

Diagnostic criteria of idiopathic hemosiderosis of the lungs

The main diagnostic criteria for idiopathic pulmonary hemosiderosis can be considered the following:

• repeatedly repeated and prolonged hemoptysis, existing;
• shortness of breath, steadily progressing as the duration of the disease increases;
• small bubble diffuse auscultative manifestations, wheezing;
• a characteristic radiographic picture - the sudden appearance of multiple focal shadows in all lung fields and a fairly rapid spontaneous disappearance (within 1-3 weeks), the development of interstitial fibrosis;
• detection in sputum of siderophages - alveolar macrophages, loaded with hemosiderin;
• hypochromic anemia, a decrease in iron in the blood;
• detection of biopsy samples of lung tissue of siderophages and interstitial fibrosis;
• negative tuberculin tests.

[21], [22], [23]

Program of examination of idiopathic hemosiderosis of the lungs

1. Common blood tests, urine tests.
2. Biochemical blood test: the content of total protein and protein fractions, bilirubin, aminotransferases, seromucoid, fibrin, haptoglobin, iron.
3. Immunological studies: the content of B- and T-lymphocytes, subpopulations of T-lymphocytes, immunoglobulins, circulating immune complexes.
4. Sputum examination: cytological analysis, determination of mycobacteria tuberculosis, atypical cells, siderophages.
5. X-ray examination of the lungs.
6. ECG.
7. Examination of the function of external respiration - spirography.
8. Ultrasound examination of the heart, liver, spleen, kidney.
9. Investigation of the lavage fluid of the bronchi: cytological analysis, the definition of siderophages.
10. Lung biopsy.

Example of the formulation of the diagnosis of idiopathic hemosiderosis of the lungs

Idiopathic hemosiderosis of the lungs, exacerbation phase, II radiographic stage, respiratory failure of II st. Chronic iron deficiency anemia of moderate severity.

[24], [25]

Differential diagnosis

Differential-diagnostic differences between idiopathic hemosiderosis of the lung and hematogenously disseminated tuberculosis

Symptoms	Idiopathic hemosiderosis of the lungs	Hematogenous disseminated pulmonary tuberculosis
Intensity of hemoptysis	Most often blood veins in sputum, sometimes intensely stained with blood sputum, marked pulmonary hemorrhage is observed rarely	Spills of blood in sputum, very often "bloody spittle", "blood clots", very often - pronounced pulmonary hemorrhage
General sputum analysis	Erythrocytes are found and in a large number of siderophages - alveolar macrophages filled with hemosiderin	A lot of red blood cells are found, siderophages are not typical, very rare
Mycobacterium tuberculosis in sputum	Do not show up	Discover
Dynamics of focal lesions in the lungs during X-ray examination	Characteristic spontaneous reverse development	Spontaneous reverse development does not happen
The appearance of cavities of decay in the lungs	Not typical	Characteristically
Study of lung tissue biopsy	Detection of a large number of siderophages and interstitial fibrosis	Siderophages are not found
Effective method of treatment	Glucocorticoid therapy	Anti-tuberculosis therapy

Differential diagnosis of idiopathic hemosiderosis of the lungs

1. Hematogenous disseminated pulmonary tuberculosis

The main manifestations of hematogenous disseminated pulmonary tuberculosis are described in the article " Pneumonia ". It is necessary to emphasize the great differential-diagnostic difficulties in connection with the generality of the symptoms of the two diseases. Hemoptysis, shortness of breath, weakness, weight loss, small bubbling rales, crepitation, disseminated focal changes in the lungs during X-ray examination are observed with both hemopoietic hemosiderosis and hematogenically disseminated pulmonary tuberculosis.

2. Lungs' cancer

Hemoptysis, anemia, increasing weakness, weight loss are forced to differentiate idiopathic hemosiderosis of the lungs with lung cancer. The basic principles of lung cancer diagnosis are outlined in the article " Pneumonia ". You should also take into account the following features:

• at a cancer in a sputum erythrocytes and cancer (atypical) are found out, at idiopathic hemosiderosis of lungs - erythrocytes and siderophages;
• with lung cancer there is never a spontaneous reverse development of radiographic signs of the disease, with hemosiderosis of the lungs focal shadows spontaneously disappear with the onset of remission;
• with central lung cancer, the expansion and fuzziness of the contours of the lung root is revealed, for idiopathic hemosiderosis, the expansion of the roots of the lungs is uncharacteristic.

3. Congestive hemosiderosis of the lungs

Hemosiderosis of the lungs can develop as a result of circulatory failure, which occurs with stagnation in a small circle. There may also be hemoptysis, and with auscultation of the lungs it is determined crepitation and small bubbling rales, in the sphincter can be determined siderophages. Congestive hemosiderosis of the lungs is diagnosed quite simply on the basis of the clinical picture of the underlying heart disease that led to stagnation in the lungs (heart defects, subsidized cardiomyopathy, cardiosclerosis, etc.) and radiographic signs of stagnation in the small circulation. There is usually no need for a lung biopsy.

4. Pneumonia

Hemoptysis, as well as blackout in the lungs of the type of focal infiltration during X-ray examination, are forced to differentiate idiopathic hemosiderosis of the lungs with pneumonia, including lobar.

5. Goodpasture Syndrome

The presence of hemoptysis, dyspnea, anemia, similar auscultatory manifestations make differential diagnostics of idiopathic hemosiderosis of the lungs and Goodpasture syndrome necessary. It is presented in the article " Goodpasture Syndrome ".

[26], [27], [28], [29], [30], [31], [32]

Treatment of the idiopathic hemosiderosis of the lungs

Treatment is as follows.

Glucocorticoid drugs are prescribed. They suppress autoimmune reactions, reduce vascular permeability. Usually, prednisalone is used in a daily dose of 30-50 mg. After improvement, the dose of prednisolone is gradually reduced (within 3-4 months) to the maintenance dose (5-7.5 mg per day), which is taken for several months.

There is a method of combined treatment with massive plasmapheresis in combination with cytostatamine. With the help of plasmapheresis, the accumulated antibodies are extracted from the plasma, and cytostatics reduce the production of new antibodies. Usually, azathioprine and schlofosfan are used. The latter is prescribed 400 mg every other day, the course of treatment is 8-10 g.

Effectively combined treatment with prednisolone, iron preparations in combination with anticoagulant and antiplatelet agents (heparin, quarantil, trental).

In connection with the development of iron deficiency anemia, patients should regularly take iron-containing preparations - ferroplex, tardiferone, conferon, etc.

With the development of a chronic pulmonary heart, treatment is aimed at reducing pulmonary hypertension.