TCM in chronic granulomatous disease. Chronic granulomatous disease

In medical terminology, granulomatosis has a dual interpretation. On the one hand, this is one of the main symptoms of complex diseases, on the other, it is an independent disease (Wegener's granulomatosis), registered in ICD-10 under code M31.3, as a necrotizing pathology from the group of systemic vasculopathies.

What is granuloma, causes of formation

The common morphological basis is the formation of granulomas. These are nodular formations consisting of proliferations of cells of different types, representing a certain type inflammatory reaction.

They can be located on the skin, mucous membranes, in the lungs, and affect the walls of blood vessels and internal organs. Accompanied by different pathological conditions, respectively, and are caused by different reasons.

It is customary to distinguish between endogenous and exogenous factors contributing to the development of granulomas.

To internal (endogenous) include products of tissue breakdown (mainly fat), impaired metabolism (urates).

External (exogenous) include:

• biological organisms(bacteria, protozoa, fungi, helminths);
• substances of organic and inorganic origin (specks of dust, smoke, medicines).

Granulomas of clear etiology are divided into infectious and non-infectious (as a result of an allergic reaction to an external antigen). The group with unknown causes includes granulomatous inflammation in sarcoidosis, biliary cirrhosis, and Crohn's disease.

Let's consider individual diseases accompanied by granulomatous growths different shapes.

Progressive discoid form

It occurs as chronic granulomatosis, another name is symmetrical pseudosclerodermiformis. Etiology unknown.

Affects the skin. Looks like flat infiltrated plaques large sizes, the color is red-yellow, the edges are clearly defined. The most common location is on both sides on the front surface of the legs.

Lipoid granulomatosis

This form was described and expanded by three doctors in the period from 1893 to 1919, which is why it was named after them - Hand-Schüller-Christian disease. Children aged 2–5 years are affected. The pathology is known for the formation of a triad of symptoms from:

• bone lesions;
• exophthalmos (bulging eyeballs);
• diabetes insipidus(occurs less often than others).

Studies have shown that lipid metabolism disorders occur secondary to damage to cells of the reticuloendothelial system in the liver, lungs, lymph nodes, spleen, bone marrow, pleura, abdominal cavity.

Manifestations of skin xanthomatosis are present in 30% of patients

Etiology unknown. Due to impaired permeability, excess cholesterol accumulates in cells (another name for the pathology is xanthomatosis).

The child gradually experiences:

• increasing weakness;
• refusal to eat;
• elevated temperature.

In 1/3 of cases, a rash of brownish and yellow dense nodules is detected on the skin; hemorrhages in the center are possible.

Bone tissue disorders are found during X-ray examination in the form of multiple defects in the bones of the skull, lower jaw, and pelvis. Less commonly in the ribs and vertebrae.

When granulomas are located on top wall orbits, bulging eyes occur on one or both sides. If destroyed temporal bone, possible deafness. Changes in the lungs are characterized by pneumonia, bronchitis, and the formation of areas of emphysema (increased airiness).

The course of the disease is subacute or chronic. At diagnosis, lipid levels are normal. Typical cells are detected by examining punctate from lymph nodes. The disease causes physical and mental retardation in the child.

Benign form of granulomatosis

Observed in sarcoidosis (Besnier-Beck-Schaumann disease). Starts more often in at a young age, predominantly women are affected. Granulomas grow in the lymph nodes, lungs, spleen, liver, rarely in bone tissue, on the skin, in the eyes.

Usually detected by chance during regular fluorography. It is asymptomatic. X-rays determine the stage of the disease from the initial enlargement of the lymph nodes to fibrosis and the formation of cavities in the lungs. Be sure to differentiate with tuberculosis.

Septicogranulomatosis of newborns

It is resistant (continues to multiply in meat products in the freezer).

View of Listeria under a microscope, a woman in labor and an infected baby secrete the pathogen in external environment within 12 days after birth, can infect medical staff

Listeria quickly spreads through the bloodstream, forms infectious granulomas and large abscesses in the internal organs and lungs. In newborns, due to a reduced protective function, it manifests itself as severe sepsis with impaired respiratory function. A mass of granulomas forms on the skin and internal organs. Other symptoms are:

• general exhaustion;
• yellowing of the skin and mucous membranes;
• hemorrhagic rashes;
• hemorrhages in internal organs, stomach, adrenal glands;
• focal manifestations from nervous system.

Infectious granulomatosis

Granulomatosis is detected in various infectious diseases. Pathogens and clinical course varies, but the presence of specific cell growths in the form of granulomas is often a mandatory accompaniment.

Granulomatosis is possible with:

• tuberculosis,
• rheumatism,
• sape,
• malaria,
• toxoplasmosis,
• actinomycosis,
• rabies,
• leprosy,
• syphilis,
• tularemia,
• typhoid and typhus,
• helminthic infection,
• scleroma,
• viral encephalitis,
• brucellosis.

The time of disappearance of granulomatous rash during typhus coincides with a decrease in temperature

The development of cell proliferation is associated with the resistance of pathogens to antibacterial drugs. Morphologically, granulomas differ in composition and structure, for example:

• In tuberculosis, the focus of necrosis is centrally located, surrounded by a shaft of epithelioid and plasma cells, lymphocytes, and single macrophages. Langhans giant cells are considered typical. Inside the giant cells contain Mycobacterium tuberculosis.
• Syphilis - represented by a significant focus of necrosis, surrounded by an infiltrate of epithelioid cells, lymphocytes, giant cells and the pathogen are found in rare cases.
• In leprosy, nodules include macrophages with mycobacteria, lymphocytes and plasma cells. Leprosy pathogens have the appearance of spherical inclusions. Granulomas easily merge and form extensive granulations.

Granulomatous diseases with necrotizing vasculitis

This is a severe form of non-infectious disease, combining signs of vascular damage (polyangiitis) with granulomatous inflammation in tissues and organs. It includes:

• necrotizing granulomatosis (Wegener's disease);
• lymphomatous granulomatosis;
• allergic vasculitis Cherdzha-Stroe;
• angiitis of the brain;
• lethal median granuloma.

The picture of granulomatous inflammation is complicated by vascular damage, which means impaired tissue trophism and a tendency to secondary infection.

When granulomas are located in the respiratory organs, there are 2 options:

• angiocentric - the main lesion concerns the vessels;
• bronchocentric - the vessels are not changed, but the granulomatous process sharply thickens the wall of the bronchi.

Wegener's granulomatosis

It is characterized by a clinical symptom complex of three types:

• necrotizing granulomatous growths in the respiratory tract;
• focal glomerulonephritis with vascular thrombosis and necrosis of loops and glomeruli;
• a generalized process with necrosis of arteries and veins, mainly located in the lungs.

Granulomatosis affects medium and small arteries, veins, and capillaries. The disease begins with an ulcerative-necrotic lesion:

• oral cavity,
• nasopharynx,
• larynx (the three listed locations are present in 100% of patients),
• bronchi,
• lung and kidney tissue (80%).

Later, the inflammatory-necrotic process spreads to other organs. Rarely affected:

• heart,
• leather,
• brain,
• joints.

When microscopying a section of tissue, giant multinucleated and epithelioid cells, granulocytes, neutrophils, eosinophils, and lymphocytes are found in granulomas. Early nodules contain many fibroblasts. Necrosis of nodules and disintegration is typical.

Scientists note that in 25% of sick children, inflammation is limited.

Clinical forms Wegener's granulomatosis depends on the extent of inflammation and damage to internal organs:

• local - covers the nasopharynx, larynx, trachea;
• limited - the disease additionally spreads to lung tissue;
• generalized - processes in any organs and systems can join.

The course of the disease is long-term (chronic), but cases of death from bleeding have been described. acute form or as a result respiratory failure.

Lymphomatous granulomatosis

Some researchers stubbornly classify it as a tumor. In addition to vasculitis, the granuloma contains atypical lymphocytes. There is information about the involvement of the Epstein Barr virus in the disease. At the same time, the autoimmune nature is emphasized. The disease affects the lungs, brain, skin, liver, and kidneys. It has a severe course. 90% of patients live no more than three years.

The nodes are painless, not fused to the skin, and may enlarge after drinking alcohol

Lymphogranulomatosis is common at all ages, men are more often affected. In the lungs, X-ray changes are determined by the type of infiltrates with decay. Eosinophilic inflammation and vasculitis in the center and periphery are found in granulomas.

The initial symptom of the disease is enlarged lymph nodes in the neck and armpits. Antibiotics are ineffective.

Further manifestations:

• general weakness;
• weight loss;
• prolonged increase in temperature.

In a blood test for lymphogranulomatosis, an acceleration of ESR and an increase in concentration are detected:

• fibrinogen;
• alpha globulin;
• haptoglobin;
• cerulloplasmin.

Allergic granulomatosis

The disease accompanies and complicates the course bronchial asthma. Accompanied by:

• growth of eosinophils in the blood;
• fever;
• increasing heart failure;
• renal failure;
• neuropathy.

Granulomatous angiitis of the brain

Another name is Horton's disease, temporal arteritis. Granulomas are located in the arteries of the head. Half of the patients have changes in the vessels of the retina, rarely in the lungs, kidneys, and liver.

The main complaint of patients is headaches. Changed vessels form aneurysms. Bleeding causes hematoma with compression of the brain matter and coma.

Lethal median granuloma

The disease is known as incurable disintegrating granuloma of the nose. Gangrene often occurs. There is an opinion that the disease should be combined with Wegener's disease. May occur:

• with a predominant inflammatory process;
• more tumor-like;
• as low-grade lymphoma.

Accompanied by severe immunodeficiency.

The ENT doctor uses dilators for examination; at the initial stage, the median granuloma is located in the nasal passages and does not destroy bone tissue

Treatment of granulomatosis

Treatment for benign granulomatosis in sarcoidosis may not be necessary if the patient is well and there is no evidence of respiratory distress.

In infectious forms and granulomatosis of newborns, large doses of broad-spectrum antibiotics are required to stop and prevent the spread of infection.

Other granulomatosis is treated:

• cytostatics (Cyclophosphamide, Methotrexate);
• corticosteroids (Prednisolone, Dexamethasone);
• radiation therapy.

For suppurative foci in the lungs, bronchoscopy is possible.

Using plasmapheresis and hemosorption, attempts are made to remove autoimmune complexes.

If renal failure develops, regular hemodialysis is necessary.

Immunoglobulin is used to restore immunity.

Timely diagnosis and treatment improve the prognosis of granulomatosis. Generalized forms are especially dangerous. The chronic course leads to permanent disability of the patient. Unfortunately, for most granulomatosis there is no effective treatment. Support therapy is used in hopes of the patient's own defenses and the possible development of new drugs.

The content of the article

Chronic granulomatosis of children is a hereditary disease characterized by recurrent infections of the skin, respiratory tract, liver and bones.
Autosomal recessive and X-linked types of inheritance of the defect are described. Mothers of sick boys often experience symptoms of discoid lupus erythematosus.

Pathogenesis of chronic granulomatosis in children

Mol. the defect is associated with insufficiency of the hexose monophosphate shunt in neutrophils and monocytes, which ensures the process of intracellular digestion associated with an increase in oxygen consumption due to the accumulation of hydrogen peroxide, nicotinamide adenine nucleotide and reduced nicotinamide adenine nucleotide. Therefore, cells cannot digest phagocytosed bacteria that do not have their own peroxidase system (staphylococci, some types of gram-negative bacteria: Escherichia, salmonella), and inactivate those types of bacteria that form peroxides (pneumococci, streptococci). It is assumed that the defect in the oxidase system is associated with the absence of cytochrome b in the plasma membrane. Defects of other enzymes have also been described: glucose-6-phosphate dehydrogenase, glutathione peroxidase, pyruvate kinase, myeloperoxidase. A typical diagnostic test for determining a defect with nitrotetrazolium: in healthy people, leukocytes reduce the colorless drug into purple formazan, which is concentrated in intracellular vacuoles; in patients, formazan is not formed. Reduced production of formazan is observed in healthy heterozygous carriers of the pathological gene.
The function of T lymphocytes in children with chronic granulomatosis is not impaired, the number of immunoglobulins and neutrophils is normal or increased, and chemotaxis is preserved. Neutrophils and monocytes are filled with phagocytosed but undigested bacteria.

Clinic of chronic granulomatosis of children

The disease in most cases develops in the first year of life, but sometimes later. It manifests itself as septic processes with multiple abscesses and inflammatory granulomas in various organs, skin, and lymph nodes. Patients, as a rule, die from septic processes; Cases of complete recovery of children who have reached the second decade have been described.
Treatment and prevention mainly consist of long-term use of antibiotics, taking into account the sensitivity of the flora. The results of immunomodulatory therapy are still uncertain.

1. Sarcoidosis (Besnier-Beck-Schaumann disease) is a chronic systemic granulomatous disease affecting many organs. In 90% of cases, the lungs are affected, as well as the lymph nodes of the bronchi, mediastinum, and neck.

Granulomatous inflammation can be found in the liver [Uvarova O.I. et al., 1982], myocardium, kidneys, bone marrow,

Rice. 29. Sarcoid granulomas in the liver. Hematoxyliomas and eosin staining. XlOO (preparation by I. P. Solovyova).

skin, mammary gland, vulva.

Sarcoidosis is a typical granulomatous disease. Its morphological substrate is epithelioid cell non-caseating granuloma (Fig. 29), the so-called sarcoid (see Chapter 2). It has now been shown that sarcoidosis is based on disturbances in the system of cell-mediated immune reactions. There are known hypotheses for the development of sarcoidosis. According to the first, an unknown factor, entering the body, activates T-lymphocytes, primarily helpers. The latter secrete lymphokines that have chemotactic activity towards blood monocytes, on the one hand, and are capable of inhibiting the migration of these cells in the area of ​​inflammation, on the other.

According to the second hypothesis, the development of the disease is based on a special form of immune deficiency of T-suppressor function. This leads to the activation of T helper cells with subsequent recruitment of monocytes to the site of damage along the above path. Indirect

Further evidence in favor of the second hypothesis of the development of sarcoid granulomas was obtained by V. Mishra et al. (1983), who studied sarcoid skin granulomas using monoclonal sera and showed that the center of the granuloma consists of macrophages and their derivatives. Among the lymphocytes surrounding the granuloma, T-helpers predominate (there are 5 times more of them than T-suppressors). In this case, T-helpers are located closer to the center of the granuloma, i.e. directly adjacent to the macrophage aggregate.

For pulmonary sarcoidosis G. Rossi et al. (1984) studied bronchoalveolar lavage cells using OKT monoclonal antibodies. The authors obtained data on the predominance of T-helper cells in the lesions. In addition, dendritic cells were found along the periphery of the granuloma.

In a sarcoid granuloma, the main cell is epithelioid, which indicates that the patient has HRT to an unknown antigen (a positive reaction to the Kveim antigen is observed). At the same time, the reaction to the purified fraction of tuberculin may be negative, which indicates an immune imbalance in the body with sarcoidosis. In the lungs of sarcoidosis there are so-called stamped non-cassifying epithelioid cell granulomas with single giant Pirogov-Langhans cells (see Fig. 4). These granulomas can form “lesion fields”, but each is separated by a ring of connective tissue, which gives the granulomas a “stamped” appearance. As a result of such a granuloma, focal sclerosis develops (a fibrous scar remains).

At the same time, perifocal alveolitis and vasculitis develop around the granuloma, which to some extent correlates with the circulation of immune complexes in the blood (they are found in 50% of patients with sarcoidosis). The most characteristic sign of sarcoidosis is capcoid granuloma, which, according to O. A. Uvarova et al. (1982), has the following morphological features: 1) clear division of granuloma into central and peripheral zones; the central one is formed by epithelioid cells, lying rather densely, and giant multinucleated cells of both types; peripheral - mainly lymphocytes, macrophages, as well as plasma cells, fibroblasts; 2) absence of exudative inflammation with perifocal nonspecific reaction; 3) absence in

center of granuloma curdled necrosis; 4) early development of annular sclerosis. Most of the signs can be found in Fig. 4 and fig. 29. Granular masses in the center, stained with eosin, may also be visible. This zone resembles fibrinoid necrosis, but is not the zone of caseous necrosis, which is characteristic of tuberculous granuloma. Sarcoid granulomas have several stages of development: a) hyperplastic; b) granulomatous; c) fibrous-hyalinous. In diagnostic terms, the second stage is most important.

Currently also known atypical forms sarcoidosis, in particular necrotizing sarcoid granulomatosis. According to E. Prugberger (1984), caverns are thin-walled apical cavities with a diameter of 2-5 cm, connected to a drainage bronchus. It is possible that nearby arterial and venous vessels with the development of microaneurysms and bleeding. In 40% of all cases of cavities, secondary fungal infection. Ulcerative sarcoidosis of the skin is unusual. S. M. Neill 1984) reported that until 1982, 27 such observations were presented in the literature, although skin lesions are observed in every fourth patient with sarcoidosis.

By 1980, 60 cases of necrotizing sarcoidosis had been published, which is characterized by a combination of granulomatous vasculitis and necrosis in the lung tissue with sarcoid-like granulomas.

M. N. Koss et al. (1980) presented an analysis of 13 observations of this syndrome. With equal frequency, unilateral and bilateral changes were noted in the lungs, which consisted of obliteration of small arteries and veins with germination of vessels and adjacent tissue with a granulomatous infiltrate of elongated macrophages (“histiocytes”), spindle-shaped and round giant multinucleated cells. Against this background, sarcoid-like granulomas were also encountered, sometimes with central coagulative necrosis. Staining for mycobacteria and fungi gave a negative result. The authors believe that this is a heterogeneous sarcoid-like group of pulmonary lesions. A special form of sarcoidosis is Löfgren's syndrome, characterized by an acute course and a triad of symptoms: bilateral adenopathy, erythema nodosum and arthralgia. This is usually a benign form of the disease, but D. Y. Hatron et al. (1985) described a case of Löfgren's syndrome with kidney damage in the form of infiltration of the interstitium with lymphocytes, plasma cells and macrophages and the development of sarcoid granulomas. Kidney damage was accompanied by renal failure and was very difficult to respond to corticosteroid therapy.

Researchers note that 80% of patients with sarcoidosis recover without treatment; Moreover, the prevalence of alveolitis is inversely proportional to the prevalence of granulomatosis.

*-B last years great attention is devoted to the study of cells obtained from bronchoalveolar lavage to diagnose the disease and clarify the stage of the process. Data on changes in cells in lavage fluid in sarcoidosis are contradictory. S. Dannel et al. (1983) observed activation of macrophages. However, there is information about the absence of such activation, which the authors judged by the expression of the C3b receptor, the content of lysosomal enzymes and the ability to adhere to glass.

Crohn's disease (granulomatous ulcer) is also a chronic granulomatous disease. The etiology and pathogenesis of the disease are not well understood. I. O. Auer (1985) believes that the increased reactivity of the T-lymphocyte system to exogenous or endogenous antigens is important in its development. The triggering factor, according to I. O. Auer

(1985), may be unknown pathogen bacterial nature, which leads to activation immune system with the development of hypersensitive cytotoxic reactions. The immunological picture of the disease is characterized by the presence of antibodies to enterocytes and intestinal tissue, the presence of T-lymphocytes sensitized to the same cells and tissues, and suppression of the function of T-suppressors. Thus, Crohn's disease is a typical form of chronic immune inflammation. This is consistent with the fact that with Crohn's disease, symptoms of rheumatoid arthritis, arthralgia, and skin lesions are simultaneously observed. In skin lesions, which occur in almost half of patients with Crohn's disease, deposits of IgA and IgM are detected in the wall of skin vessels. Along with earcoid-like granulomas, the skin may have changes such as polymorphic erythema and erythematous-vesicular-godermatitis.

The main morphological substrate of Crohn's disease are granulomas that arise in the mucous membrane and in the deeper layers of any part of the gastrointestinal tract, but more often in the ileocecal region (Fig. 30), with necrosis of granulomas and the formation of ulcers.

According to K. Geboes (1985), Crohn's disease is primarily characterized by damage to the lamina propria, regardless of the location of the lesion along the gastrointestinal tract (esophagus, stomach, duodenum, ileum and part small intestine and colon). In addition, in Crohn's disease, changes were found in the intestinal nervous system: axonal hyperplasia with vasoactive polypeptide, on the one hand, and axonal necrosis, on the other.

Granuloma in Crohn's disease is built according to a general plan: its main cells are markers of the immune response - epithelioid cells located around a center consisting of an amorphous material. Macrophages, lymphocytes, and plasma cells are localized along the periphery, and closer to the center, Pirogov Langhans cells. Early changes in Crohn's disease begin with small

Rice. 30. Granulomatous reaction in the bottom of a small intestinal ulcer in Crohn’s disease.

Staining with hematoxylin and eosin (preparations L.L.

Capullera).

a - loose epithelioid cell granuloma with a giant multinucleated cell of mixed type. X250; b - the same granuloma with a giant multinucleated Pirogov-Langhans cell. X600.

ulcerations of the epithelium covering hyperplastic Peyer's patches (group lymphatic follicles). Using immunocytochemical research methods, a gradual increase in the content of plasma cells producing IgG, IgM, and IgA was established. In addition, rapid accumulation of plasma cells synthesizing IgE was noted along the edges of ulcerations. Granulomas begin to form along the edges of ulcerations and in the depths of Peyer's patches. At the same time, in the cytoplasm of macrophages forming granuloma, the presence of immune complexes - IgG and complement - is noted, and in the cytoplasm of granulocytes - E. coli antigens. Apparently, in the focus of granulomatous inflammation, activation of macrophages occurs due to both immune complexes and breakdown products of granulocytes that have phagocytosed foreign material, as in the formation of granulomas in the liver in cases of candidal infection.

The participation of immune mechanisms in the pathogenesis of granulomatous inflammation in Crohn's disease is indicated by the following immune phenomena that have clinical and diagnostic significance: the presence of antibodies (against the epithelium of the colon); lymphocytes, enterobacteria, circulating immune complexes in the blood and antibody-mediated cytotoxicity. The cytotoxic activity of one's own lymphocytes increases, apparently associated with the function of normal killer lymphocytes against the epithelium of the colon. Nevertheless, granulomas in Crohn's disease are formed on the basis of HRT, although the mechanisms of HNT also participate in the development of inflammation, but they recede into the background. Usage electron microscopy complemented the clinical and morphological picture of Crohn's disease. The surgical material showed the constant participation of inflammatory cells in the inflammatory process. Their number increases, they intensively degranulate and secrete biologically active substances, accumulating in intestinal tissues: histamine, slow-reacting substance of anaphylaxis (leukotrienes), prostaglandins. Accumulation in tissues of catecholamines released from the disintegrating elements of the autonomous intramural nervous system was noted. The accumulation of all these substances leads to increased tension in the smooth muscles of the intestinal wall, impaired motility and increased inflammation.

There is ongoing debate in the literature about the relationship between Crohn's disease and chronic ulcerative colitis. According to the morphological picture, these are two completely various diseases. Crohn's disease is an immune granulomatosis that can be localized in any part of the gastrointestinal tract - from the esophagus to the rectum. In this disease, the cellular inflammatory infiltrate is dominated by cells involved in immune inflammation, lymphocytes and macrophages, while in chronic ulcerative colitis - neutrophils. Biochemical analysis of enzyme markers of inflammatory infiltrate cells in both nosological forms also showed significant differences between them. The marker of lymphocytes and macrophages (5-nucleotidase) was absent in all examined patients with ulcerative colitis. In tissue cell homogenates of the intestinal wall in patients with ulcerative colitis, neutrophil enzymes were found in large quantities: myeloperoxidase, lysozyme, vitamin Bi2-binding protein. Only when the rectum was involved in the process in patients with Crohn's disease were neutrophil marker substances found, and even then in small quantities . In all other cases, only 5-nucleotidase was found. Not only the nature of the inflammation (granulomatous in Crohn's disease and purulent in ulcerative colitis), but also a number of other signs indicate the presence of immune inflammation in the first case and its lack of expression in the second case. second. Thus, in Crohn's disease, a specific immunoreactive protein was discovered in the homogenate of intestinal tissue, which is detected using the serum of people with Crohn's disease. In ulcerative colitis this protein is absent. The fact of generalization of lesions in Crohn's disease is undoubtedly important. Thus, according to O Barduagni et al. (1984), skin lesions in the form of sarcoid-like granulomas or vasculitis occur in almost half of the patients. P. Dhermy et al. (1984) described granulomatous conjunctivitis with the formation of an epithelioid granuloma with giant multinucleated cells. More often, authors began to describe cases of vaginal lesions in patients aged 13-35 years. At the same time, epithelioid cell granulomas in areas of inflammation various departments intestines were combined with chronic nonspecific inflammatory infiltration or with the formation of epithelioid granulomas in the vaginal wall. M Kramer et al. (1984) note that extraintestinal lesions in Crohn's disease can occur in the oral cavity, skin, liver, muscles, and bones. J. McClure (1984) described a case of granulomatous lesions of the gallbladder in a 64-year-old patient with Crohn's disease. Granulomatous lesions of the stomach were identified by Z. Antos et al. (1985). A. H. T. Sumathipola (1984) observed the formation of a penile ulcer with sarcoid granulomas at its edges. Thus, Crohn's disease is a systemic granulomatous process. Its fundamental difference from sarcoidosis is that with Crohn's disease, the main changes occur in the gastrointestinal tract, while intestinal lesions are not typical for sarcoidosis.

Necrotizing vasculitis with granulomatosis. This group of diseases, according to J. J. Chanda and J Collen (1984), includes: a) Wegener's granulomatosis; b) lymphomatous granulomatosis; c) allergic granulomatous vasculitis Churg - Stross; d) granulomatous angiitis of the brain; e) lethal median granuloma. The presence of immunopathological reactions with the participation of immune complexes, as well as angiitis with tissue trophic disorders inherent in this process and the addition of a secondary infection leaves a certain imprint on the picture of granulomatous inflammation. In addition, some of them (lymphomatous granulomatosis, types of lethal median granuloma) can be classified as lymphoproliferative, i.e. to tumor processes.

Depending on the predominant localization of lung lesions, angiocentric and bronchocentric variants of granulomatous processes are distinguished (Churg A., 1983]. With the latter, the vessels are not affected, while the bronchial wall is sharply thickened and compacted due to granulomatous inflammation.

G p a n u l e m a t o z B e g e n e p a. B. Wiesner (1984), based on data from F. Wegener (1936), identifies the following clinical symptom complex characteristic of Wegener's granulomatosis: 1) necrotizing granulomatous processes in the respiratory tract; 2) focal glomerulonephritis with necrosis and thrombosis of individual glomerular loops and granulomatous changes in the glomerulus; 3) generalized focal necrotizing vasculitis with damage to arteries and veins, which is expressed mainly in the lungs [see. also Weiss M. A., Crissman J. D., 1984].

H. E. Yarygin et al. (1980) believe that the most characteristic morphological changes with Wegener's granulomatosis, they are observed in arteries of medium and small caliber (Fig. 31). Moreover, depending on the caliber of the vessel and the stage of the process, the prevalence and form of vascular lesions may vary, however, there is usually a consistent change of alterative, exudative and proliferative processes, and depending on the predominance of certain processes, destructive, destructive-productive and productive arteritis are distinguished. Damage to veins and capillaries is also typical.

These vascular lesions are combined with granulomatous inflammation. Granulomas develop primarily in areas of necrotic and necrotic-ulcerative lesions of the oral cavity and nose, larynx, trachea, lungs, pharynx, and later in the generalization phase in other organs and tissues.

The sizes and cellular composition of granulomas are different. In them, along with epithelioid cells, giant multinucleated symplasts and cells of the Pirogov-Langhans type and foreign bodies(see Fig. 31) neutrophilic and eosinophilic granulocytes and lymphocytes are determined. The authors, however, note that in the “fresh”\c~>iiiiiienim Barr) . At the same time, the importance of the immune complex mechanism of tissue damage is emphasized, apparently with the participation of autoantibodies.

A l l e p g i h e s k i y g p a n u l e m a t o z. This variant of necrotizing vasculitis (Churg-Strauss disease) was described by A. Churg and Strause in 1951. The authors studied a group of 13 patients with this syndrome. The disease occurred with asthma, fever, hypereosinophilia in the peripheral blood, heart and kidney failure, and peripheral neuropathy. All patients died.

A pathomorphological examination revealed necrotizing vasculitis of predominantly small arteries with the presence of eosinophilic infiltration and granulomatous reaction both in the vascular wall itself and around the vessel, as well as signs of fibrinoid necrosis. These lesions were associated with extravascular granulomatous foci. Apparently, the important fact is that the disease begins with attacks of bronchial asthma and hypereosinophilia. Both men and women get sick equally often; usually these are middle-aged people. Half of the patients have both diffuse and focal pneumonic infiltrates. The basis of organ changes, based on materials from Ya. Lung-Legg and M. A. Legg (1983), is the presence of vasculitis and granulomas. In the latter, there may be central eosinophilic necrosis, around which polysadically distributed macrophages, epithelioid cells, giant multinucleated cells, as well as eosinophilic granulocytes are localized. Some authors, including E. M. Tareev and E. N. Semenkova (1979), consider this disease as a variant of nodose periargeritis. Thus, S. Pedailles et al. (1982), when studying severe forms of periarteritis nodosa, identified 3 patients whose disease was characterized by corticosteroid-dependent asthma, hypereosinophilia, as well as the presence of intra- and extravascular necrotizing granulomas. The authors consider these observations to be an example of periarteritis nodosa. At the same time Ya. Lung-Legg and M. A. Legg (1983) emphasize the presence of HRT mechanisms in the development of the immunopathological process; the antigen that causes it has not yet been identified: it may be a virus, bacteria or a drug.

Granulomatous giant cell arteritis of the brain (granulomatous giant cell arteritis) was described in 1932. Currently, the disease is also called temporal (temporal) ) arteritis, or Horton's disease. The pathological basis of the disease, according to H. E. Yarygin et al. (1980), is a granulomatous inflammation of the arteries of the musculelastic and muscular types of the head. At the same time, the authors identify several stages of the process: 1) dystrophic changes in the vascular wall that occur due to increased vascular permeability in the form of mucoid swelling of arterial walls, foci of fibrinoid necrosis; 2) actual granulomatous inflammation with the formation of tuberculoid type granulomas. In half of the cases, according to R. Warzok et al. (1984), the process involves the retinal arteries and optic nerves, damage to the arteries of the lungs, kidneys, liver, adrenal glands, and fatty tissue is also possible [Yarygin H. E. et al., 1980]. R. Warzok et al. (1984) observed a 25-year-old patient with acute headache, meningitis was suspected. After the final diagnosis was made, treatment with corticosteroids was carried out. Death occurred 2.5 years later as a result of a cerebral coma. An autopsy revealed round cell infiltrates in all parts of the brain with an admixture of giant cells such as foreign bodies and fibrinoid necrosis in the arteries. The formation of granuloma-like foci of lymphocytes, neutrophilic and eosinophilic granulocytes, macrophages, and epithelioid cells was noted. Cerebral coma was caused by intraventricular hematoma, which was associated with disruption of the structure of the elastic framework, including veins, and the formation of microaneurysms in capillaries and veins.

The materials presented in the monograph by H. E. Yarygin et al. (1980), show the role of immune complexes in damage vascular walls; the deposits apparently may include IgG, IgA, IgM. The cause of the appearance of immune complexes can be viral antigens, in particular the surface antigen of the hepatitis B virus.

L et al nasal granuloma is also called incurable necrotizing granuloma of the nose, Stewart's nasal granuloma, or gangrenous granuloma. Isolated into an independent nosological form by I. P. Stowoort (1933). However, researchers are currently questioning the possibility of such an isolation. Indeed, according to the materials of J. Michaels and A. Gregory (1977), there are three groups of patients suffering from a severe gangrenous-proliferative process localized in the nasal area, more precisely along the midfacial line: the first - primary inflammatory processes; the second - distinct tumor processes; the third is lymphoma with a low degree of malignancy. A similar point of view is shared by M. Collini et al. (1984), who propose to combine Wegener’s granulomatosis, malignant reticulosis and nasal lymphoma into “granulomatous syndrome of the midfacial line”.

As follows from the data of H. E. Yarygin et al. (1980), M. Mirakhur et al. (1983), diffuse cellular infiltration with lymphocytes, macrophages, plasma cells, neutrophilic and eosinophilic granulocytes is observed in the affected area. Against this background, according to H. E. Yarygin et al. (1980), a combination of destructive-productive venulitis and capillaritis develops with disruption of tissue trophism, the addition of a secondary infection and the development of gangrene or purulent melting of tissue. This histological picture reflects the presence of severe immune deficiency, but the nature of the latter is currently unclear.

Of particular interest is the observation of M. Mirakhur et al. (1983), who noted a combination of signs of Stewart's nasal granuloma, histiocytic medullary rheumatoidosis and Wegener's granulomatosis (deposition of IgA deposits in the capillaries of the renal glomeruli).

Thus, necrotizing angiitis with granulomatosis represents a heterogeneous group of diseases, some of them may be related to tumor processes. In this regard, it should be noted that there is a group pathological processes, for which pathologists use the concept of “pseudotumor” and which represent special form inflammatory infiltrate, close (if not identical) to granulomatous inflammation. At the same time, there are relatively benign tumor growths of macrophages (in the literature these growths are designated as histiocytic), called “granulomas” and

discussed in the section “Granulomatous diseases” [Vizner B., 1984]. These forms will be discussed briefly in the next section of the chapter.

Tumor and pseudotumor forms of “granulomatoses”. Research by L. Narasimhorao et al. (1984) showed that inflammatory pseudotumors are reactive inflammatory growths of a benign nature. They are detected in the lungs, sometimes in the liver, stomach, rectum, parotid gland, nasal and oral cavity, heart, renal pelvis and in the mesentery. K. L. Narasinharao et al. (1984) distinguish the xanthogranulomatous type of such tumors with a predominance of “histiocytes”, plasma cell granulomas and sclerosing pseudotumors.

The authors described a pseudotumor of the appendix measuring 7x5 cm in an 8-year-old boy. Histological examination revealed an inflammatory infiltrate of plasma cells in the wall of the appendix. cells and eosinophils, foci of calcification. I. Tirina et al. (1986) observed a 19-year-old patient whose disease progressed with moderate fever, thrombocytosis, hypochromic anemia, polyclonal hypergammaglobulinemia, increased ESR, and weight loss. A tumor-like formation with a diameter of 7 cm was found at the edge of the mesentery, which was excised during surgery. Histologically and immunomorphologically a plasma cell granuloma of plasma cells was detected varying degrees differentiation, fibrocytes, smooth muscle cells. After the operation, clinical symptoms returned to normal. In a 45-year-old patient, a pseudotumor of the mesenteric root was a manifestation of Whipple's disease. G. S. Zenkevich et al. (1986) described 4 patients with the specified brain damage. In three cases after the death of the patients, a pathological examination revealed tumor-like foci: two in the cerebral hemispheres, one in the brain stem. Referring to literature data, the authors indicate that the lesions were tumor-like in nature and were often localized in the white matter of the cerebral hemispheres, often periventricularly. Histological, according to literature data and materials of G.S. Zenkevich et al. (1986), the lesions consisted of lymphocytes, macrophages, and plasmatic cells. Blood vessels were found in the center and periphery of the lesion. Granulomas of loosely arranged epithelioid cells with single giant multinucleated Pirogov-Langhans cells and foreign bodies were associated with the vessel wall. Granulomas were also found near massive cellular infiltrates of the structure described above. The authors regard this pathology as “granulomatous encephalitis.”

Great difficulties arise when analyzing a group of diseases currently known as histiocytosis X. B. Wiesner (1984) under this name combines three diseases: eosinophilic granuloma, Hand-Schüller-Christian disease and Abt-Letterer-Siwe disease. There are other classifications: acute disseminated histiocytosis X (Abt-Letterer-Siwe disease), chronic or subacute histiocytosis X (Hand-Schueller-Christian disease) and focal histiocytosis X (eosinophilic granuloma).Morphologically, these diseases differ from each other, but in all cases there is a proliferation of cells of monocytic origin, which are conventionally called histiocytes [Vizner B., 1984] Although B. Wiesner classifies histiocytosis X as a typical granulomatosis, the International Classification of Tumors presents separately “eosinophilic granuloma” and “histiocytosis X.” Closer to tumor process, apparently, there is an eosinophilic granuloma. The latter can develop in the bones and internal organs, in particular in the lungs. According to the observations of B. Wiesner (1984), in the lungs there are poorly demarcated accumulations of “histiocytes” with a large number of eosinophilic granulocytes. Macroscopically, these infiltrates can be diffuse and nodular. Giant multinucleated cells are detected. Necrosis and fibrous changes may occur in the nodes. The histological picture may resemble changes characteristic of lymphogranulomatosis. The other two forms of histiocytosis X appear to be closely related. In fresh lesions, along with “histiocytes,” macrophages are found containing lipids in the cytoplasm, often cholesterol (therefore, the lesions have an ocher color), as well as plasma cells, eosinophils and fibroblasts. Giant multinucleated cells may also occur. A feature of “histiocytes” in histiocytosis X is the presence in their cytoplasm of Birbeck granules, or X-granules, the characteristics of which are given in Chapter 2 when describing the Langerhans cells of the skin. This also correlates with the identification of a specific S-IOO protein. However, it was shown that this protein (and, therefore, granules) is not strictly specific for histiocytosis X.

This protein is also found in bronchial cartilage, myoepithelium of bronchial glands, and nerve fibers. The authors also analyzed the diagnostic value of detecting Langerhans cells containing Birbeck granules in various lung lesions, including eosinophilic granuloma. They showed that individual typical Langerhans cells are found in the lungs in many diseases, but in eosinophilic granuloma such cells form aggregates in the interstitium of the lungs. This work casts doubt on the diagnostic value of detecting Langerhans cells in bronchoalveolar lavage. A similar point of view is held

F. S. Kullberg et al. (1982), who observed an eosinophilic granuloma in a 28-year-old patient, in whom numerous nodular formations in the lungs were detected by X-ray. An open lung biopsy revealed nodules of macrophages (histiocytes) and eosinophils. Electron microscopic examination of granuloma cells revealed Birbeck granules. Previously prepared ultrathin sections of lavage cells and tissue treated during transbronchial biopsy were retrospectively studied (the initial result of the study was negative, i.e., no Langerhans cells were detected). Upon repeated examination, Langerhans cells were found in both samples. The authors point out the relative value of identifying these granules in lavage cells and transbronchial lung biopsies. Nevertheless, observations show that these granules have an important, albeit indicative, diagnostic value.

Malakoplakia. Malokoplakia is one of the poorly studied forms of granulomatous diseases. More often, this disease affects the urinary tract, especially the mucous membrane of the bladder, less often the process is localized in the interstitium of the kidney. In this case, flat yellow nodules are found in the bladder. Light microscopy reveals granulomatous inflammation with an accumulation of macrophages having PAS-positive granules in the cytoplasm and various shapes formations containing calcium (Michaelis-Gutmann bodies). These bodies, when seen by electron microscopy, have a characteristic structure with concentric electron-dense cores and pale outer zones. Some researchers associate the development of malakoplakia with a defect in the function of macrophages, which do not digest phagocytosed material.

Along with lesions of the urinary tract, lesions of the gastrointestinal tract, endometrium, testicle, prostate gland.

A. Flint and T. Murad (1984) observed lesions in the pharynx and stomach. Infiltrates of their lymphocytes, macrophages, plasma cells and eosinophils were detected. Characteristic was the presence of macrophages with cytoplasmic PAS-positive granularity, as well as unusual crystals in expanded ZEM tanks. In one observation, Michaelis-Gutmann bodies were detected. In the observation of D. R. Radin et al. (1984) the lesion was localized in the area colon. Of great interest is the observation of M. Nistal et al. (1985), which were found in a polyp removed from

maxillary sinus, accumulations of marophages containing basophilic granules in the eosinophilic cytoplasm, giving positive reaction for calcium. Using electron microscopy, the authors identified a typical structure of granules, also called “bull’s eye”. It has been noted that the development of malocoplakia is facilitated by a violation immune status the body when using immunosuppressive drugs. When describing endometrial malocoplakia confirmed by electron microscopy, S. Chadha et al.

(1985) showed the presence in the cells of a granulomatous lesion of not only Michaelis Tutman bodies, but also Escherichia coli.

E. Crouch et al. 1984) presented a case of a tumor-like form of malocoplakia. A 54-year-old patient died of thromboembolism pulmonary artery. At autopsy, it was discovered that the tissue of the left kidney was replaced by tumor-like growths of gray-yellow color with areas of necrosis. Similar nodes were found in the left lung. On light microscopy, the growths consisted of macrophages with a small number of plasma cells and neutrophilic leukocytes. Michaelis-Gutman bodies, characteristic of malakoplakia, were found in the cytoplasm of macrophages.

Other granulomatous diseases of unknown etiology. P e c i d i v i v e l i x o p a d o c t i o n and t - Weber-Christian disease. The disease is characterized by abundant dense nodules in the subcutaneous adipose tissue [Lever U. F., 1958]. Usually there are three

stages. The first is the stage of acute inflammation, the second is the stage of the appearance of macrophages, when there is a limited infiltrate of macrophages with foamy cytoplasm, multinucleated cells are found, the third is the fibroplastic stage. W. F. Lever (1958) points to the possibility of systemic lesions in the third stage. We observed such damage to the subcutaneous fatty tissue in one patient [Tyukov A.I.]: among the fields of fibrous tissue there were foci of granulomatous inflammation (Fig. 32, a). These lesions are small epithelioid cell granulomas, sometimes with Pirogov-Langhans giant cells and transitional type cells. Foci of lymphocytic infiltration and groups of fat cells were also detected. Productive inflammation was often localized near small arteries

Rice. 52. Non-suppurating recurrent paniculitis.

Staining with hematoxylin and eosin (preparations by V. A. Odinokova and A. I. Tyukova).

a-in the subcutaneous fatty tissue epitelnoid cell granulomas with giant multinucleated cells are visible. X400; b-periarterial localization of epithelioid cell granuloma. X 400.

Rice. 33. Granuloma annulare: granulomatous reaction around dystrophically altered collagen (indicated by an arrow).

Hematoxylin and eosin staining. X 80 (preparation by V. A. Odinokova and A. I. Tyukova).

riy fiber (rie. 32.6), the wall of which was thickened and infiltrated with lymphocytes. The presence of epithelioid granulomas and vasculitis indicates the role of hypersensitive mechanisms in the development of the disease.

Ring-shaped, or ring-shaped, granuloma is usually localized on the skin of the hands and feet, the rash consists of small dense pale red nodules [Lever U.F., 1958], which tend to group into circles and rings. Histological examination reveals focal degeneration of collagen with deposition of mucin between degenerated collagen fibers, in the focus of complete degeneration of collagen fibers - an area of ​​coagulation necrosis, along the periphery of the foci of degeneration - lymphocytic infiltration, as well as giant multilayer cells of foreign bodies not associated with the zone of necrosis [Lever U F., 1958]. This structure of the granuloma is clearly visible on the microslide presented by A.I. Tyukov (Fig. 33): in the middle of the lesions there is a structureless zone of necrosis (1), to which dense eosinophilic material such as keratin is present (2); Macrophages and Pirogov-Langhans giant cells are visible along the periphery of the lesion. R. J. FernarukT et al. (1981) described a patient with a generalized granuloma annulare: there were maculopapular rashes with a depression in the center on the skin of the flexor surface of the arms, neck, abdomen and legs. Light microscopy of skin biopsies revealed areas of basophilic degeneration of collagen fibers in the dermis, stained with alyshan blue. Macrophages and single multinucleated cells were visible around such fibers. In the observation of R. H. Packer et al. (1984) annular granuloma appeared 8 months after herpes zoster in the scar area. During histological examination, the authors found foci of degeneration and necrosis of collagen, surrounded along the periphery by palisade-shaped macrophages (histiocytes). The authors indicate that annular (annular) granuloma can occur after tuberculin tests, insect bites, trauma, and insolation.

Sometimes chronic inflammation with the appearance of giant cells can occur around areas of elastic fiber degeneration, for example in the skin after sunburn. A. P. Ferry et al. (1984) described similar granulomatous inflammation around foci of elastosis in the conjunctiva.

K s an to g p a n u l e m a t o s y, or l i l i p o g p a - n u l e m a t o s y, is a group of pathological processes in which formation of granuloma is observed with the participation of adipose tissue or in it itself. Typically *liprogranulomas are built from accumulations of histiocytes, macrophages, phagocytizing decaying elements of adipose tissue. The cytoplasm of macrophages becomes foamy due to the presence of droplets of phagocytosed fat in it. Such macrophages with foamy cytoplasm are called xanthoma cells. Microscopically, xanthogranulomas are built from clusters of xanthoma cells located among layers of fibrous connective tissue. In addition to xanthoma cells, lymphocytes, polynuclear cells, plasma cells, histiocytes and multinucleated giant cells of the Touton type are found in large numbers. These are cells that occupy an intermediate position between giant cells of foreign bodies and cells of the Pirogov-Langhans type. Xanthogranulomas usually lack epithelioid cells, markers of the immune mechanism of granuloma formation; xanthogranulomas belong to the group of non-immune toxic-infectious granulomas. Xanthogranulomatous inflammation has been described quite often in recent years. Thus, in addition to skin lesions, xanthogranulomatous pyelonephritis, cholecystitis, endometritis, osteomyelitis, and prostatitis have been described.

Among spontaneously occurring xanthogranulomatosis of adipose tissue, the so-called granulomatous febrile non-suppurating panniculitis (inflammation of adipose tissue) deserves special attention. This generalized lipogranulomatosis occurs in the form of two syndromes: Weber-Christian syndrome and Rothmann-Makai syndrome. The first occurs with frequent relapses and with fever, the second occurs without fever and is more mild. Morphologically, both syndromes are close to each other: patients develop multiple nodes on the skin. The histological structure of the nodes corresponds to xanthogranuloma with the only peculiarity that, along with xanthogranulomas, epithelioid cell granulomas and vasculitis are found in the nodes, which indicates the participation of immune mechanisms in their formation. All processes of immune formation are more clearly expressed in Weber-Christian syndrome. With the latter, lipogranulomas are found in the mesentery and retroperitoneal tissue. The so-called juvenile xanthogranulomatosis occurs and is described in detail in the literature. This disease can appear in newborns and usually manifests as multiple xanthogranulomatous nodules in the subcutaneous tissue of the neck and head, and (less commonly) throughout the trunk and extremities. In some cases, the nodes may disappear without any trace, which is not observed in adults. In addition, in adults, xanthogranuloma nodes are often solitary. The histological structure of xanthogranulomas in adults and children is identical. In rare cases, both children and adults experience visceral manifestations of xanthogranulomatosis with damage to the retroperitoneal tissue and mesentery. The cause of generalized xanthogranulomatosis remains unclear. Drug-induced xanthogranulomas arising in connection with subcutaneous injection fat emulsions (subcutaneous xantho- or olegranulomas) or those occurring in the lungs when inhaling aerosols due to upper respiratory tract disease.

They are described in detail by A. A. Abrikosov, the first in our country to pay attention to the so-called oleopneumonia - oleogranulomas in the lungs of patients who inhaled aerosols. In 1927, A. A. Abrikosov described in detail the morphology of subcutaneous oleogranuloma, expressed a THOUGHT about the ischemic nature of FAT IH-KpIJBOB M proposed to distinguish four types of subcutaneous oleogranuloma: artificial, or injection, traumatic, parainflammatory, spontaneous (with typhus).

Xanthogranulomatous lesions of the kidneys and pelvis are common. Thus, M. A. Parsons et al. (1983) studied this disease in 87 patients (72 of them were women). People aged 45-65 years are most often affected. Histologically, along with the phenomena of chronic inflammation, which is focal in nature (yellowish foci), an accumulation of foamy macrophages containing cytoplasmolipids (xanthoma cells) is observed.

The authors identify several stages of the process and believe that in the third stage typical granulomas with giant multinucleated cells can be detected. Cases of xanthogranulomatous cholecystitis have also been described (about 100 cases). They are detected in the form of nodes in the wall of the bile duct, consisting of foamy macrophages, giant multinucleated cells with an admixture of lymphocytes, neutrophils, eosinophils. The authors indicate that xanthogranulomatosis is promoted by chronic infection, as well as violations of the patency of the excretory pathways.

Along with xanthogranulomatous processes, cases of lipogranulomatous liver lesions of unknown origin have been described. Thus, M. E. Keen et al. (1985) reported on 2 patients with multiple liver lipogranulomatosis of unknown etiology. Granulomas were localized in the area of ​​the central veins and consisted of macrophages, giant multinucleated cells, and lymphocytes. There were drops of fat. This lesion was accompanied by veno-occlusion syndrome.

V. Cruickshank (1984) and V. Cruickshank et al. (1984) studied the possible mechanisms of lipogranulomatosis of the liver and spleen. The authors examined organ tissues taken during autopsy operations in 1970-1972. and for 1946-1955. (for comparison) and found an increase in cases of inclusion of mineral oils in the tissues of the spleen, lymph nodes, porta hepatis, mesentery, mediastinum, as well as in the liver in the 70s.

In this case, the formation of sarcoid-like granulomas or changes similar to Whipple's disease was observed. The authors believe that mineral oils can be ingested from food packaging and penetrate into internal organs through the intestinal wall.

More often there are publications about idiopathic e-c and X p a n u l e m a t o n x lesions of internal organs. Thus, a number of researchers have studied granulomatous inflammatory foci in the prostate gland. In 1984, more than 30 such observations were described in the American literature alone. Typically, these granulomas are detected several months after surgery on the prostate gland; they have an area of ​​necrosis in the center, which is surrounded by palisade-shaped elongated macrophages (histocytes) and giant multinucleated cells.

There are different opinions about the cause of the development of granulomas. In particular, S. Mies et al. (1984) believe that their appearance reflects the response of HRT to collagen damage. B 1985 A. Mbakop presented a literature review describing 53 cases of so-called nonspecific granulomatous prostatitis. However, analysis of the material indicated that it was about chronic inflammation with lymphocytic and plasmacytic infiltration, and not about granulomatous inflammation.

Possible development of idiopathic granulomatous orchitis. As with other idiopathic organ injuries, it is necessary to exclude the infectious etiology of granulomatous inflammation, as well as other forms, in particular malakoplakia (pathognomonic for the latter Michaelis-Gutman bodies). In the observation of F. Algoba et al. (1984) a patient with numerous minor injuries to the genital organs developed inflammatory process in the right testicle, due to the ineffectiveness of antibiotic therapy, the testicle was removed. Light microscopy revealed focal infiltration of testicular tissue with lymphocytes and monocytes with an admixture of rare giant multinucleated cells and individual neutrophilic granulocytes.

According to J. D. van der Walt et al. (1985), granulomatous inflammation of unknown origin can also develop in the salivary glands. Granulomatous gastritis has been described, as well as the appearance of granulomatous allergic nodules in the conjunctiva.

The latter occur in healthy young children in the form of a small yellowish nodule. The center of the nodule is occupied by a focus of necrosis, intensely stained with eosin; Along its periphery there are epithelioid cells, giant cells and single eosinophilic granulocytes. We observed a macrophage granuloma with giant cells in the wall of the removed gallbladder (see Fig. 4).

Melkersson-Rosenthal syndrome is of great interest. At the same time, they believe that “it is possible to identify diseases in which a pronounced proliferation of SFM cells is observed. Such processes are called histiocytosis and are divided into tumor and reactive (benign). The latter can be caused by known or unknown etiological factors, in particular viruses, fungi, inorganic substances: salts of beryllium, zirconium, etc. Specified point point of view is interesting and promising. It allows us to consider both typical granulomatous reactions and acute infectious “granulomas” in one group. At the same time, this approach does not exclude the possibility of identifying a group of epithelioid cell granulomas among reactive histocytoses.

A number of researchers propose to sharply narrow the concept of “granulomatous inflammation”. Thus, W. Feigl et al. (1981) using computer analysis, studied more than 63 thousand descriptions of biopsies based on materials from the Department of Pathological Anatomy of the University of Vienna. According to these authors, “granuloma” was found in 0.7% of all biopsies, most often in sarcoidosis. The authors believe that the concept of “granuloma” should be limited to epithelioid granulomas, excluding from it the reaction to foreign bodies. Such granulomas differ not only in their morphological originality, but also in the presence of cell-mediated immune mechanisms of their formation.

It should be noted that when diagnosing the form of granulomatous inflammation and the nature of the granulomatous disease, it is advisable to carry out a diagnostic analysis in several stages. At the first stage, it is desirable to identify the histological form of granulomatous inflammation (mature macrophage granulomas or epithelioid cell granulomas). The histological signs of granulomatous processes given in the book will help with this. The histological form of granulomas will largely make it possible to classify each specific case of granulomatous inflammation as one or another group of diseases. Thus, noncaseating epithelioid cell granulomas are found in sarcoidosis, exogenous allergic alveolitis, and berylliosis; epithelioid cell granulomas with caseous necrosis - in tuberculosis; epithelioid cell granulomas with suppuration in the center - with mycoses, leishmaniasis. The first stage of diagnosis can be carried out in any pathology department, and it is advisable to adhere to the description scheme given in the appendix.

The second stage of diagnosis is to accurately determine the etiological factor. The monograph presents the main etiological factors of granulomatous inflammation: a separate chapter is devoted to each related group of etiological agents. This diagnostic stage requires the use of additional research methods, in addition to morphological ones: bacteriological, immunological, immunomorphological, spectrographic. It can be carried out primarily in specialized medical institutions and pathological bureaus. Establishing the etiology of granulomatous inflammation is extremely important for clinicians, as it determines therapy. Thus, for granulomatous diseases of infectious etiology, the main task of treatment is to eliminate the pathogen as soon as possible.

In granulomatous diseases of non-infectious etiology, establishing the etiological factor is no less important, since early elimination of contact with it can stop the progression of the process. Finally, for granulomatous diseases of unknown etiology, corticosteroid therapy is effective, and in some cases, cytostatic therapy.

The third stage of diagnosis is to identify the immunopathological mechanisms of granuloma formation, the rate of cell renewal in the inflammation, which requires the presence of reagents, in particular monoclonal antibodies, for the differentiated identification of types of macrophages, lymphocytes, as well as the use of autoradiography and other methodological techniques.

We hope that the proposed scheme for diagnostic analysis of foci of granulomatous inflammation will be useful for practitioners.

Granulomatous diseases are a heterogeneous group of diseases (nosological forms) of various etiologies, the structural basis of which is granulomatous inflammation. These diseases have a number of characteristics in common: the presence of granulomatous inflammation; disturbance of immunological homeostasis; polymorphism of tissue reactions; penchant for chronic course with frequent relapses; frequent vascular damage in the form of vasculitis.

Classification. Based on the etiology of the disease. There are: granulomatous diseases of established etiology:

Granulomatous diseases of infectious etiology (rabies, viral encephalitis, cat scratch disease, typhus, paratyphoid fever, typhoid fever, yersiniosis, brucellosis, tularemia, glanders, rheumatism, rhinoscleroma, tuberculosis, syphilis, leprosy, malaria, toxoplasmosis, leishmaniasis, actinomycosis, candidiasis, schistosomiasis, trichinosis, alveococcosis);

Granulomatous diseases of non-infectious etiology (silicosis, talcosis, aluminosis, berylliosis). Listed diseases belong to the group of pneumoconiosis, diseases caused by exposure to industrial dust, and will be discussed in Chapter. "Occupational diseases";

Granulomatous diseases of unknown etiology (sarcoidosis, Crohn's disease, rheumatoid arthritis, Wegener's granulomatosis, Weber-Christian panniculitis, xanthogranulomatous pyelonephritis, giant cell granulomatous de Quervain's thyroiditis).

Sarcoidosis (Besnier-Beck-Schaumann disease) is a chronic systemic granulomatous disease affecting many organs, however, the lungs with hilar and mediastinal organs are most often affected. lymph nodes (90%).

The morphological substrate of sarcoidosis is an epithelioid cell granuloma, whose structure is very similar to tuberculosis, however, there is no caseous necrosis in it (Fig. 48 on color incl.). The outcome of such granuloma is usually hyalinosis. Sometimes granulomas have two more characteristic histological features: lamellar deposits of lime and proteins - Schaumann bodies; star-shaped inclusions are steroid bodies. These formations are found in the cytoplasm of giant cells.

Crohn's disease (granulomatous-ulcerative ileocolitis) is a chronic granulomatous disease, the etiology and pathogenesis of which have not been established.

The main morphological substrate of the disease is granuloma, which occurs in the mucous membrane and deeper layers of the wall of any part of the gastrointestinal tract, but more often in the ileocecal region. Granuloma in Crohn's disease is built according to general principle: its main cells are markers of the immune response - epithelioid cells located around the center of necrosis. Further outwards there are macrophages, lymphocytes, granulocytes and plasma cells. Pirogov-Langhans cells are located closer to the center. Most often such changes are found in the terminal section ileum. The entire thickness of the intestinal wall is affected, which becomes swollen and thickened. The mucous membrane appears lumpy, resembling a cobblestone street, which is associated with alternating narrow and deep ulcers located in parallel rows along the length of the intestine with areas of normal mucous membrane.

Horton's disease (giant cell temporal arteritis) is a disease of the elastic and muscular type(mainly the temporal and occipital arteries) with damage to the medial tunicum of the vessels.

Elderly people are more often affected. There is an opinion about the infectious-allergic nature of the disease, and there is also a genetic predisposition to this arteritis in people with expression of the BU4 antigen.

Histologically, necrosis of muscle fibers and elastic membranes is detected in the affected vessels. Around necrotic foci, a productive reaction develops with the formation of granulomas from plasmatic, epithelioid and giant cells of the Pirogov-Langhans type or cells of foreign bodies. In the intima of blood vessels, loose connective tissue grows, which leads to narrowing of the lumen of the vessel and thrombus formation.

Wegener's granulomatosis is a systemic necrotizing vasculitis with granulomatosis predominantly of medium- and small-caliber arteries, as well as microvasculature vessels of the respiratory tract and kidneys. Persons of both sexes are affected; the clinical picture includes symptoms of pneumonitis, chronic sinusitis, ulceration of the nasopharyngeal mucosa, and kidney damage.

Vascular changes in Wegener's granulomatosis consist of three phases: alterative (necrotic), exudative and productive with a pronounced granulomatous reaction. The outcome is sclerosis and hyalinosis of blood vessels with the development of chronic aneurysms or stenosis up to complete obliteration of the lumen. In arteries of medium caliber (muscular type), endarteritis is more often found, and in small-caliber arteries - panarteritis. The vessels of the microvasculature are affected with great consistency (destructive and destructive-productive arteriolitis, capillaritis). The damage to these very vessels underlies the formation of granulomas, which merge to form fields of granulomatous tissue that undergo necrosis. Necrotizing granulomatosis is first detected in the upper respiratory tract, which is accompanied by a picture of nasopharyngitis, saddle-shaped deformation of the nose, sinusitis, frontal sinusitis, ethmoiditis, tonsillitis, and stomatitis.

Pathognomonic is purulent inflammation with the formation of ulcers and bleeding. In some cases, these symptoms are the only manifestation of the disease (localized form of Wegener's granulomatosis). As it progresses, a generalized form develops with the formation of necrotizing granulomatosis in the trachea, bronchi, and lung tissue. In addition to the respiratory tract, granulomas can be found in the kidneys, skin, joints, liver, spleen, heart and other organs.

Granulomas developing in and outside the vessels are similar to those in periarteritis nodosa, but in them with granulomatosis

Wegener's necrosis develops, sometimes with a cavity in the central part. Granulomas are surrounded on the outside by fibroblasts, among which there are giant cells and leukocytes.

As a result of granulomatous lesions, sclerosis and organ deformation develop.

A characteristic feature of Wegener's granulomatosis is glomerulonephritis, which is usually represented by mesangioproliferative or mesangiocapillary forms with fibrinoid necrosis of capillary loops and glomerular arterioles and extracapillary reactions (formation of characteristic crescents).

Weber-Christian granulomatous panniculitis (WPC) is a rare nodular panniculitis. Panniculitis is a limited productive inflammation of the subcutaneous tissue. The main signs of GPVC are recurrent course, fever, localization in subcutaneous tissue lower extremities, as well as the most diverse composition of inflammation foci (histiocytes with foamy cytoplasm, lymphocytes, neutrophils, giant multinucleated cells).

Xanthogranulomatous pyelonephritis is a rare type of chronic productive interstitial nephritis, one of the characteristic features of which is the presence of foci of xanthoma cells in the renal tissue. Xanthoma (foam) cells are characterized by foamy cytoplasm, in which multiple small lipid droplets are revealed when stained for lipids with Sudan. Sometimes giant multinucleated cells of the xanthoma type are found.

Foci of xanthomatosis alternate with lymphoplasmacytic infiltrates with an admixture of polymorphonuclear leukocytes. Based on morphological data, two forms of xanthogranulomatous pyelonephritis are distinguished: diffuse (most common) and nodular (tumor-like).

The disease is more common in women aged 30-50 years, but there are observations of it in childhood.