Hystiocytosis X of the lung: causes, symptoms, diagnosis, treatment

Hystiocytosis of the lungs (histiocytic lung granulomatosis, eosinophilic granuloma, pulmonary granulomatosis X, histiocytosis X) is a disease of the reticulogistiocytic system of unknown etiology, characterized by the proliferation of histiocytes (cells X) and the formation of histiocytic granulomas in the lungs and other organs and tissues.

Pulmonary granulomatosis from Langerhans cells is a monoclonal proliferation of these cells in the interstitium and air spaces of the lung. The causes of histiocytosis of the X lung are unknown, but smoking is of paramount importance. Manifestations are shortness of breath, cough, fatigue and / or pleural pain in the chest. Diagnosis is based on history, radiation studies, bronchoalveolar lavage flushing and biopsy. Treatment of histiocytosis X of the lungs involves the cessation of smoking. Glucocorticoids are prescribed in many cases, but efficacy is unknown. Lung transplantation is effective if combined with a cessation of smoking. The prognosis is generally favorable, although patients have an increased risk of malignant tumors.

The disease of lung histiocytosis X occurs at a frequency of 5 per 1 million inhabitants. Men and women suffer equally often. In women, the disease develops later, but any differences in the timing of the occurrence of the disease in the representatives of different sex may reflect differences in attitude towards smoking.

[1], [2], [3]

What causes histiocytosis of the X lungs?

Causes of the disease are unknown. Pathogenesis has been studied quite insufficiently. The importance of autoimmune mechanisms in the development of histiocytosis X is not excluded. Pulmonary granulomatosis from Langerhans cells is a disease in which monoclonal CD1 a-positive Langerhans cells (a subtype of histiocytes) infiltrate bronchioles and interstitium alveoli, which are found in combination with lymphocytes, plasma cells, neutrophils and eosinophils . Pulmonary granulomatosis X is one of the manifestations of histiocytosis from Langerhans cells, which can affect the organs in isolation (most often - the lungs, skin, bones, pituitary gland and lymph nodes) or simultaneously. Pulmonary granulomatosis X occurs isolated in more than 85% of cases.

A characteristic pathomorphological feature of the disease is the formation of peculiar granulomas and systemic lesions of organs and tissues. Most often granulomas are found in the lungs and bones, but in addition, they can be localized in the skin, soft tissues, liver, kidneys, gastrointestinal tract, spleen, lymph nodes. The main cells of the granuloma are histiocytes originating from the bone marrow.

Distinguish the acute form of histiocytosis X (Abta-Leggerer-Sieve disease) and the primary chronic form (Hvda-Schuller-Krischen disease).

The acute form is characterized by an increase in lungs in the volume, the formation of a number of cysts up to 1 cm in diameter, microscopic examination determines granulomas from histiocytes, eosinophils, and plasma cells.

In the chronic course of histiocytosis X, many small nodules can be seen on the surface of the lungs, pleural overlaps, emphysematous swellings resembling cysts are identified, on the incision the lungs have a honeycomb structure. When microscopic examination of the lungs at early stages, granulomas are detected, consisting of histiocytes, plasma cells, eosinophils, and lymphocytes. In the subsequent early enough formed cystic formations, emphysematous thin-walled bulls. Characteristic is also the development of fibrous tissue.

Pathophysiological mechanisms can include the increase and proliferation of Langerhans cells under the action of cytokines and growth factors secreted by alveolar macrophages in response to cigarette smoke.

Symptoms of histiocytosis of the lungs X

Typical symptoms of lung histiocytosis X - dyspnea, unproductive cough, fatigue and / or pleural pain in the chest, 10-25% of patients develop sudden spontaneous pneumothorax. Approximately 15% of patients do not develop symptoms, and the latter is detected accidentally during chest radiography performed for another reason. Bone pain due to the development of cysts (18%), skin rashes (13%) and polyuria due to diabetes insipidus (5%) are the most common extrapulmonary manifestations found in 15% of patients, rarely being the symptoms manifested by histiocytosis of the X lungs. Symptoms of histiocytosis of the lungs are meager; the results of a physical examination are usually normal.

Abta-Letterter-Sieve disease (acute course of histiocytosis X) occurs mainly in children under 3 years of age and has the following main manifestations:

• acute onset of the disease with high body temperature, chills, severe cough (usually dry and painful), dyspnea;
• rapid generalization of the pathological process with the appearance of clinical signs of damage to bones, kidneys, skin, central nervous system (meningeal syndrome, severe encephalopathy);
• possibly the development of purulent otitis.

A lethal outcome is possible within a few months.

Primary chronic formahistiocytosis X (Heta-Schuller-Krystchen disease) occurs mainly in young people, usually aged 15-35 years.

Patients complain of such symptoms of histiocytosis of the X lung, as: shortness of breath, dry cough, general weakness. In some patients, the disease begins with sudden acute pain in the chest, which is due to the development of spontaneous pneumothorax. Perhaps an absolutely asymptomatic onset of the disease and only a random fluorographic or radiographic examination reveals changes in the lungs. In connection with the defeat of the bone system by the granulomatous process, bone pain may appear, most often the bones of the skull, pelvis, and ribs are affected. Destruction of the Turkish saddle is also possible. In this case, the hypothalamic-pituitary zone is damaged, the secretion of the antidiuretic hormone is disrupted and a clinic of diabetes insipidus arises - pronounced dry mouth, thirst, frequent profuse urination, with a light urine with low relative density (1.001-1.002 kg / l).

When examining patients, acrocyanosis is determined, the thickening of the terminal phalanges in the form of "drum sticks" and nails in the form of "watch glasses". These symptoms of lung histiocytosis X are particularly pronounced with prolonged disease and severe respiratory failure. Many patients have xantelasms (lipid yellow spots in the eyelid, usually the upper ones). When the spine is injured, one can detect its curvature. When percussion of the bones of the skull, ribs, pelvis, spine, painful points are determined. Histiocytic infiltration of the orbit causes the appearance of exophthalmos in some patients. It should be noted that a one-way exophthalmos is possible.

With percussion of the lungs, the usual clear pulmonary sound is determined, with development of emphysema - boxed, when pneumothorax appears - tympanic sound. With auscultation of the lungs, a characteristic sign is the weakening of vesicular breathing, less often dry rales, and very rarely crepitation in the lower parts. With the development of pneumothorax, breathing in its projection is absent.

When involved in the pathological process of the liver, there is an increase in it, a slight soreness. It is possible to increase the spleen, lymph nodes.

The kidney damage is manifested by a decrease in the amount of urine, possibly the development of acute renal failure.

Diagnosis of histiocytosis of the lungs X

Histiocytosis X of the lung can be suspected on the basis of history, physical examination and chest X-ray; confirmation of the disease is performed with high-resolution CT (CTWR), bronchoscopy with biopsy and bronchoalveolar lavage.

Radiography of chest organs demonstrates classical bilateral symmetrical focal infiltrates in middle and upper pulmonary fields with the presence of cystic changes with normal or enlarged lung volume. The lower parts of the lungs are often not affected. The onset of the disease may be similar to that in COPD or lymphangioleiomyomatosis. Confirmation of the presence of cysts in the middle and upper lobes (often bizarre forms) and / or focal lesions with thickening during CTWR interstitium is considered pathognomonic for histiocytosis of X lungs. In the study of the function, there may be no abnormalities, or there may be restrictive, obstructive or mixed changes, depending on the period of the disease being performed. Often the diffusion capacity for carbon monoxide (DLC0) is reduced, which reduces the tolerance of exercise.

Bronchoscopy and biopsy are performed in cases where ray methods and lung function studies are uninformative. Detection of CDIa cells in bronchoalveolar lavage fluid, which is more than 5% of the total number of cells, has a high specificity for this disease. Histological examination of the biopsy material reveals the proliferation of Langerhans cells with the formation of a small number of clusters of eosinophils (structures previously defined as eosinophilic granulomas) in the center of the fibrotic cells that may have a stellate configuration. Immunohistochemical staining is positive for CDIa cells, S-100 protein and HLA-DR antigens.

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Laboratory diagnostics of histiocytosis of the lungs X

1. General blood test : acute forms of the disease are characterized by anemia, leukocytosis, thrombocytopenia, increased ESR. In the chronic form of the disease, there are no significant changes, but many patients have an increase in ESR.
2. The general analysis of urine - in acute form of the disease, as well as with kidney damage in chronic course, proteinuria, cylindruria, and microhematuria are detected.
3. Biochemical blood test: in the acute form of the disease appears a biochemical inflammation syndrome (an increase in the level of seromucoid, sialic acids, a1-, a2- and y-globulins); it is possible to increase cholesterol, copper, and in the malignant course of the disease, the activity of the angiotensin-converting enzyme increases. The defeat of the liver is accompanied by an increase in the level of bilirubin, alanine aminotransferase, with the development of acute renal failure - increases the content of creatinine and urea.
4. Immunological research. Specific changes, as a rule, no. There may be an increase in the level of immunoglobulins, circulating immune complexes, reduction of T-suppressors and natural killers.
5. Investigation of lavage fluid bronchus: characterized by lymphocytosis and an increase in the number of T-suppressors.

Instrumental diagnosis of histiocytosis of the lungs X

• X-ray examination of the lungs. Usually, 3 radiological stages of the disease are isolated.

The first stage is characteristic of the early phase of histiocytosis X. Its main manifestations are the presence of bilateral shallow focal shadows against the background of intensification of the pulmonary pattern. Small focal shadows correspond to the proliferation of histiocytes and the formation of granulomas. An increase in the intrathoracic lymph nodes is not observed.

The second stage is characterized by the development of interstitial fibrosis, which is manifested by a fine-meshed (small-mesh) pulmonary pattern.

The third stage (the final stage) is manifested by cystic-bullous formations with the picture of "cellular lung", expressed by fibro-sclerotic manifestations.

• A superficial or open biopsy of the lungs is performed for the purpose of final verification of the diagnosis. In biopsies, a characteristic feature of the disease is a granuloma, consisting of proliferating histiocytes. In the 2nd and 3rd stages of the disease, biopsy is not performed, as it is usually not possible to detect granulomas.
• Examination of the function of external respiration. Violation of the ventilation function is detected in 80-90% of patients. A restrictive type of respiratory failure is typical (a decrease in LEL, an increase in the residual volume of the lungs). There is also a violation of bronchial patency, as indicated by the decrease in FEV, and the Tiffno index (ratio FEV1 / ZHEL), a decrease in the volume of the maximum space velocity of 25, 50 and 75% YEL (MOS 25, 50, 75).
• Investigation of the gas composition of blood. A decrease in the partial pressure of oxygen is characteristic.
• Fibrobronchoscopy. There are no specific and significant changes in the bronchi.
• Perfusion lung scintigraphy. Characterized by a sharp violation of microcirculation, determined areas of sharply reduced blood flow.
• Computer tomography of the lungs. Thin-walled cystic-bullous formations of various sizes are determined. They are located in all parts of the lungs.
• ECG. With the development of emphysema, the deviation of the electric axis of the heart to the right can be observed, the rotation of the heart around the longitudinal axis in a clockwise direction (deep teeth S in virtually all chest leads).

Diagnostic criteria for histiocytosis of the lungs X

The main diagnostic criteria for the primary chronic form of histiocytosis X can be considered:

• recurrent pneumothorax;
• restrictive and obstructive ventilation disorders;
• the possibility of systemic damage to organs and tissues;
• formation of "cellular lung" (it is revealed roentgenologically);
• detection of histiocytic granuloma in biopsy specimens of lung tissue.

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Treatment of histiocytosis of the lungs X

The main component of treatment is the cessation of smoking, leading to the resolution of symptoms of the disease in about a third of patients. As with other IBLARBs, the empirical use of glucocorticoids and cytotoxic agents is a frequent practice even considering that their effectiveness has not been proven. Lung transplantation is the method of choice in safe patients with increasing respiratory failure, but the disease can recur in the transplant if the patient continues to smoke.

Spontaneous disappearance of symptoms occurs in some patients with minimal manifestations of the disease; five-year survival rate - approximately 75%, median survival of patients - 12 years. However, in some patients, slow progression of the disease develops, for which clinically significant prognostic factors are the duration of smoking, age characteristics, the presence of multiple organ dysfunction, persistent symptoms of lung histiocytosis X, indicating the generalization of the process, numerous cysts on chest radiograph, DL decrease, FEV / FVC (<66%), high residual volume ratio (00) to total lung capacity (> 33%) and long-term erapii glucocorticoids. The cause of death is respiratory insufficiency or the development of malignant tumors. The increased risk of lung cancer is due to smoking.