Actinomycosis

What is actinomycosis?

Actinomycosis (synonyms: radiovascular fungal disease; Aktinomykose – German .; actinomycose – French) is a chronic disease caused by various types of actinomycetes. It is characterized by lesions of various organs and tissues with the formation of dense infiltrates, which then suppurate with the appearance of fistulas and a kind of skin lesion.

Causes of Actinomycosis

Pathogens – various types of actinomycetes, or radiant fungi. The main ones are the following: Actinomyces Israeli, Actinomyces bovis, Actinomyces albus, Ac. violaceus. Actinomycetes grow well on nutrient media, forming colonies of irregular shape, often with radiant edges. Pathogens for many species of farm and laboratory animals. In the pathological material found in the form of drusen, which are yellowish lumps with a diameter of 1-2 mm. Microscopy in the center of the drusen is an accumulation of mycelium filaments, and on the periphery – a flask-like bulges. When stained with hematoxylinoosin, the central part of the druse turns blue and the flask pink. There are drusen, in which the border of the flask-shaped cells is missing. Actinomycetes are sensitive to benzylpenicillin (20 U / ml), streptomycin (20 μg / ml), tetracycline (20 μg / ml), chloramphenicol (10 μg / ml) and erythromycin (1.25 μg / ml).
Epidemiology. Actinomycosis is common in all countries. They get sick people and farm animals. However, cases of human infection from sick people or animals are not described.

Causative agents of actinomycosis are widely distributed in nature (hay, straw, soil, etc.). Actinomycetes are often found in healthy people in the oral cavity, plaque, tonsil lacunae, and on the mucous membrane of the gastrointestinal tract. Both exogenous and endogenous modes of infection matter.

Pathogenesis during actinomycosis

The most common is the endogenous pathway of infection. Actinomycetes are widely distributed in nature, in particular on plants, can get into the body with plants and be on the mucous membranes as a saprophyte. The transition of actinomycetes from a saprophytic to a parasitic state is facilitated by inflammatory diseases of the mucous membranes of the oral cavity, respiratory and gastrointestinal tract. At the site of the introduction of actinomycetes, an infectious granuloma is formed, which grows into the surrounding tissues. In granulations, abscesses arise which, breaking through, form fistulas. Skin lesions are secondary in nature.

A secondary, mainly staphylococcal infection also plays a role in the formation of suppuration. Radiation fungus antigens lead to specific sensitization and allergic restructuring of the body (delayed or tuberculin type hypersensitization), as well as to the formation of antibodies (complementary, agglutinins, precipitin, etc.).

Symptoms of Actinomycosis

The duration of the incubation period is unknown. It can fluctuate over a wide range and reach several years (from the time of infection to the development of manifest forms of actinomycosis). The main clinical forms of actinomycosis: actinomycosis of the head, tongue and neck; torokalny actinomycosis; abdominal; actinomycosis of the urinary organs; skin actinomycosis; mycetoma (Madur foot); actinomycosis of the central nervous system. Actinomycosis refers to primary chronic infections with a long progressive course. With the growth of infiltration the skin is involved in the process. Initially, a very dense and almost painless infiltration is determined, the skin becomes cyanotic-purple, a fluctuation appears, and then a nonhealing fistula develops. In pus detect whitish-yellowish small lumps (Druze).

The neck-maxillofacial form is most common. According to the severity of the process, it is possible to distinguish a deep (muscular) form, when the process is localized in the intermuscular fiber, subcutaneous and cutaneous forms of actinomycosis. In muscular form, the process is localized mainly in the masticatory muscles, under the fascia covering them, forming a dense infiltration of cartilage consistency in the region of the mandible angle. The face becomes asymmetrical, and a trisism of varying intensity develops. Then, in the infiltrate, foci of softening appear, which spontaneously open, forming fistulas that separate the purulent or bloody-purulent fluid, sometimes with an admixture of yellow grains (drusen). Cyanotic coloration of the skin around the fistula is long lasting and is a characteristic manifestation of actinomycosis. On the neck, peculiar skin changes are formed in the form of transverse rollers. In cutaneous form of actinomycosis, infiltrates are spherical or hemispherical, localized in the subcutaneous tissue. Trism and chewing disorders are not observed. Skin form is rare. The actinomycous process can trap cheeks, lips, tongue, tonsils, trachea, orbits, and larynx. The course is relatively favorable (compared to other forms).

Thoracic actinomycosis (actinomycosis of the chest cavity and chest wall), or actinomycosis of the lungs. The start is gradual. There are weakness, low-grade fever, cough, dry at first, then with mucopurulent sputum, often with blood (sputum has the smell of earth and taste of copper). Then a picture of peribronchitis develops. Infiltration spreads from the center to the periphery, captures the pleura, chest wall, skin. There is swelling with an extremely pronounced burning pain during palpation, the skin becomes purple-bluish. Fistulae develop, pusicles of actinomycetes are found in the pus. Fistula communicates with the bronchi. They are located not only on the chest, but may appear on the back and even on the thigh. For heavy. Without treatment, patients die. In terms of frequency, the torus actinomycosis takes the second place.

Abdominal actinomycosis is also quite common (ranked third). Primary foci are more often localized in the ileocecal region and in the area of ​​the appendix (over 60%), then there are other sections of the colon and very rarely affects the stomach or small intestine, the esophagus.

The abdominal wall is affected again. Primary infiltrate is most often localized in the ileocecal region, often imitating surgical diseases (appendicitis, intestinal obstruction, etc.). Spreading, infiltration captures other organs: the liver, kidneys, spine, can reach the abdominal wall. In the latter case, there are characteristic skin changes, fistula, communicating with the intestines, usually located in the inguinal region. In rectal actinomycosis, infiltrates cause the occurrence of specific paraproctitis, fistulae are opened in the perianal region. Without etiotropic treatment, mortality reaches 50%.
Actinomycosis of the genital and urinary organs is rare. As a rule, these are secondary lesions in the spread of infiltration in abdominal actinomycosis. Primary actinomycous lesions of the genital organs are very rare.

Actinomycosis of bones and joints is rare. This form occurs either as a result of the transition of actinomycous infiltrate from neighboring organs, or is the result of hematogenous drift of the fungus. Osteomyelitis of the bones of the leg, pelvis, spine, and lesions of the knee and other joints are described. Often the process is preceded by injury. Osteomyelitis occurs with the destruction of bones, the formation of sequesters. It is noteworthy that, despite the pronounced bone changes, patients retain the ability to move, with damage to the joints, the function is not seriously impaired. When fistulas form, characteristic skin changes occur.

Actinomycosis of the skin occurs, as a rule, for the second time during the primary localization in other organs. Changes in the skin become noticeable when actinomycous infiltrates reach the subcutaneous tissue and are especially characteristic during fistula formation.

Mycetoma (maduromatosis, madurian foot) is a peculiar variant of actinomycosis. This form was known for a long time, quite often met in tropical countries. The disease begins with the appearance on the foot, mainly on the sole, of one or several dense delimited nodes the size of a pea and more, covered first with unchanged skin, later on the seals the skin becomes red-violet or brownish. Next to the original nodes, new ones appear, the skin swells, the foot increases in volume, changes its shape. Then the nodes are softened and opened with the formation of deep-reaching fistulas that emit purulent or serous-purulent (sometimes bloody) fluid, often with a foul odor. In the discharge, small grains are usually yellowish in color (drusen). Nodes are almost painless. The process slowly progresses, the entire sole is knotted, the toes are turned upwards. Then the nodes and fistulous passages appear on the rear foot. The whole foot turns into a deformed and pigmented mass penetrated by fistulas and cavities. The process can go to the muscles, tendons and bones. Sometimes there is atrophy of the muscles of the leg. Usually the process captures only one foot. The disease lasts a very long time (10-20 years).

Complications. Layering of secondary bacterial infection.

Diagnosis of Actinomycosis

In advanced cases with the formation of fistulas and characteristic skin changes, the diagnosis is not a diagnosis. It is more difficult to diagnose the initial forms of actinomycosis.

Some value for the diagnosis has an intracutaneous test with actinolysate. However, only positive and sharply positive samples should be taken into account, since weakly positive intradermal tests are often found in patients with dental diseases (for example, in alveolar pyorrhea). Negative results of the test do not always allow to exclude actinomycosis, since in patients with severe forms they can be negative due to a sharp inhibition of cellular immunity; they are always negative in people with HIV. Isolation of the culture of actinomycetes from sputum, mucous membrane of the pharynx, nose does not have diagnostic value, since actinomycetes are often found in healthy individuals. Diagnostic value has RSK with actinolysate, which is positive in 80% of patients. The greatest diagnostic value is the selection (detection) of actinomycetes in pus from fistulas, in biopsy specimens of affected tissues, in druses, in the latter only mycelium filaments are sometimes microscopically detected. In these cases, one can try to isolate a culture of actinomycetes by sowing material on Sabur’s medium.

Actinomycosis of the lungs must be differentiated from neoplasms of the lungs, abscesses, and other deep mycoses (aspergillosis, nocardiosis, histoplasmosis), and also from pulmonary tuberculosis. Abdominal actinomycosis has to be differentiated from various surgical diseases (appendicitis, peritonitis, etc.). The defeat of the bones and joints – from purulent diseases.

The diagnosis of human actinomycosis is mainly based on the isolation and identification of causative agents, because clinical symptoms are often misleading and histopathology and serology are low-specific and low-sensitivity. The presence of drusen, which sometimes give pus the appearance of semolina, should initiate a search for actinomycetes. However, given that only 25% of specimens of actinomycotic pus contain these granules, their absence does not exclude the diagnosis of actinomycosis.

Collection and transportation of pathogenic material.
Patmaterial – pus, suitable for bacteriological analysis of actinomycosis, discharge from fistulas, bronchial secretion, granulation and biopsy specimens. During the fence, precautions should be taken against contamination of congenital, mucosal, microflora. In all cases, whenever possible, pus or tissue should be obtained by percutaneous puncture. For the diagnosis of thoracic actinomycosis, bronchial secretion must be obtained transtracheally.

Sputum examination is unreliable because it usually contains actinomycetes of the oral cavity, including pathogenic varieties. A transthoracic percutaneous biopsy or a percutaneous puncture of suspicious abdominal abscesses is often the only means of obtaining satisfactory specimens of the material for diagnosis. Transportation of samples to the bacteriological laboratory should be fast enough. If long-term transportation is unavoidable, special transport media such as Stuart’s medium should be used, although fermenting actinomycetes are less susceptible to oxidative damage than strict anaerobes.

Microscopic examination
When drusen are present, this makes it possible to quickly and relatively reliably make a preliminary diagnosis after an inspection at a low magnification (d 100) of an actinomycotic granule placed under the coverslip and with methylene blue added to a drop of 1%. Actinomycotic friends appear as cauliflower-like particles with an unpainted center and blue periphery, in which white blood cells and short strings, sometimes with clubs, come from the center of the granules. Gram-stained smears obtained by squeezing the granules between two glasses show filamentous, branching, gram-positive structures that represent pathogenic actinomycetes, as well as a variety of other gram-negative and gram-positive bacteria that indicate the presence of concomitant microorganisms. The presence of these bacteria is necessary to distinguish actinomycotic druses from granules formed by various aerobic actinomycetes (Nocardia, Actinomadura, Streptomyces), which never contain the accompanying microflora. Direct and indirect immunofluorescence for the detection of specific antibodies can also be used to determine the varieties of actinomycetes that are in the granule, without isolating the culture.

Cultural diagnostics
To obtain reliable results, it is advisable to use transparent media so that the cups can be carefully scanned to detect characteristic filamentous colonies, and grow a culture for at least 14 days. Cultures can be examined every 2-3 days without changing anaerobic conditions, if the Fortner method (1928) is used to obtain a low oxygen potential. If anaerobic flasks or cups are used, it is advisable to plant two or three media at the same time to examine them to determine the growth of actinomycetes after 3, 7, and 14 days. Since the removal of the cups from the anaerobic environment usually stops the further growth of microorganisms that need prolonged incubation without changing anaerobic conditions.

Preliminary results of the culture study are obtained in 2-3 days, when under the microscope one can see characteristic arachnid microcolonies of A. israelii, A. gerencseriae or P. propionicum. Confirmation of preliminary microscopic or early culture diagnoses by unequivocal identification of a pathogenic actinomycete variety may take 14 days or more. This is necessary to reliably identify differences between the fermenting actinomycetes and morphologically similar contaminants obtained from the mucous membranes of the patient, as well as similar aerobic actinomycetes of the genera Nocardia, Actinomadura and Streptomyces. Detailed bacteriological analysis of concomitant microflora may also be useful for selecting the appropriate antibiotic therapy.

Molecular methods, such as genetic studies or polymerase chain reactions (PCR), are currently only being developed and may in the future be able to allow faster diagnosis of actinomycosis.

Serological diagnosis
Actinomycotic infection does not necessarily stimulate the humoral immune response, which can be detected by existing laboratory methods. However, none of the methods used with a wide variety of antigens used yielded satisfactory results due to sensitivity and specificity problems (Holmberg, Nord and Wadstrm 1975, Holmberg 1981, Persson and Holmberg 1985).

Treatment of Actinomycosis

The best results are obtained by a combination of etiotropic therapy (antibiotics) and immunotherapy (actinolysate). When the neck-maxillofacial form prescribed inside phenoxymethylpenicillin at 2 g / day and with a course of not less than 6 weeks. You can also prescribe tetracycline in large doses (0.75 g 4 times a day for 4 weeks or 3 g per day only in the first 10 days, and then 0.5 g 4 times a day for the next 18 days) . Erythromycin is prescribed 0.3 g 4 times a day for 6 weeks. With abdominal forms and with lung actinomycosis, large doses of benzylpenicillin (10,000,000 U / day or more) are administered intravenously for 1–1.5 months, followed by switching to phenoxy-methylpenicillin at a daily dose of 2–5 g for 2–5 months . With the layering of secondary infection (staphylococcus, anaerobic microflora) prescribed long courses of dicloxacillin or tetracycline antibiotics of the group, with anaerobic infection – metronidazole. For immunotherapy, actinolysate can be administered subcutaneously or intradermally, as well as intramuscularly. Under the skin and intramuscularly injected in 3 ml of actinolysate 2 times a week. In the course – 20-30 injections, the duration of the course is 3 months. With an abscess, empyema, surgical treatment is performed (dissection and drainage). When extensive damage to the lung tissue is sometimes resorted to lobectomy. Of the antibiotics, tetracyclines are the most effective, followed by phenoxymethylpenicillin and erythromycin less effective. Actinomycetes strains resistant to these antibiotics were not found.

Forecast. Without etiotropic treatment, the prognosis is serious. In abdominal actinomycosis, 50% of patients died, and all patients died in the thoracic. The cervico-maxillofacial actinomycosis was relatively easier. All this necessitates the early diagnosis and initiation of therapy before the development of severe anatomical damage. Given the possibility of relapse, convalescents should be under long-term observation (6-12 months).

Prevention of Actinomycosis

Oral hygiene, timely dental treatment, inflammatory changes in the tonsils and oral mucosa. Specific prevention is not developed. Activities in the outbreak do not hold.

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