Inflammatory diseases of the jaws. Odontogenic osteomyelitis of the jaw: clinical guidelines

List of Abbreviations

SCO – secondary chronic osteomyelitis

CT – Computed Tomography

WBCI – white blood cell intoxication index

PT – physical therapy

MC – medical care

MRI – magnetic resonance imaging

MSCT – multislice computed tomography

НПВС – non-steroidal anti-inflammatory and antirheumatic drugs

PCO – primary chronic osteomyelitis

ESR – erythrocyte sedimentation rate

US – ultrasound examination

MFR – maxillofacial region

EOD – electrical pulp testing of the tooth

EchoCG – echocardiography

EEG – electroencephalography

Terms and Definitions

• Osteomyelitis is an inflammatory condition of bone tissue of various etiologies that begins in the medullary cavity and rapidly spreads through the Haversian system, involving the periosteum and adjacent soft tissues in the inflammation.

• Periostitis is an inflammatory disease involving the periosteum of the alveolar process and the body of the jaw originating from an odontogenic or non-odontogenic focus.

• Sequestrum is a demarcated inflammatory-necrotic focus of bone tissue that lies more or less freely and does not undergo autolysis.

• Rehabilitation is a system of state, social, economic, medical, vocational, and other measures aimed at preventing the development of diseases and complications leading to temporary or permanent disability, and reintegrating patients and individuals with disabilities into society.

• Dentoalveolar segment is a conventional unit of volume of the alveolar part of the jaw used to assess the extent of the infectious and inflammatory process. The lower boundary of the dentoalveolar segments of the posterior mandible is the mandibular canal (canalis mandibulae), and of the anterior region, a virtual horizontal plane connecting the mental foramina (foramen mentale dex. et sin.). The upper boundary of the dentoalveolar segments of the maxilla is the floor of the nasal cavity and maxillary sinuses.

• Vincent's sign is decreased sensitivity of the skin over the affected area and/or the lower lip.

1. Brief information on the disease or condition

1.1 Definition of the disease or condition

Chronic osteomyelitis is purulent destructive or proliferative inflammation of bone tissue lasting more than 4 weeks, characterized by the formation of sequestra or the absence of a tendency to spontaneous recovery with progressive resorptive and productive changes in the bone tissue and periosteum.

Chronic periostitis of the jaw is a chronic odontogenic infectious-inflammatory process in which the spread zone may extend beyond the periodontium of a single dentoalveolar segment, including the periosteum that served as the portal of entry for the pathogen.

Primary chronic osteomyelitis (non-suppurative) is a fibro-osseous proliferative disease without an identified etiologic trigger, characterized by the absence of pus formation, fistula, and sequestration, with a stubbornly recurrent course and the formation of excess bone tissue in the affected area.

Secondary chronic osteomyelitis is purulent destructive or proliferative inflammation of bone tissue lasting more than 4 weeks associated with odontogenic infection, the presence of foreign bodies, trauma, bone developmental defects, or systemic diseases, characterized by necrosis of mineralized and bone tissues, suppuration, resorption, sclerosis, and hyperplasia.

Chronic recurrent multifocal osteomyelitis (non-suppurative) is a chronic non-infectious disease characterized by periods of exacerbations and remissions and the formation of multifocal lytic bone lesions.

SAPHO syndrome (Synovitis, Acne, Pustulosis, Hyperostosis, Osteitis) is a type of chronic recurrent multifocal osteomyelitis in adults associated with synovitis, acne, pustulosis, hyperostosis, and osteitis.

1.2 Etiology and pathogenesis of the disease or condition (group of diseases or conditions)

Primary chronic osteomyelitis is a non-bacterial chronic inflammatory disease of unknown etiology, which may also be associated with other conditions, including autoimmune diseases and syndromes such as SAPHO syndrome, Majeed syndrome, and cherubism [7, 45]. A response to a bacterial stimulus, as well as chronic periostitis resulting from muscle hyperactivity, is considered as an etiological factor [53]. A potential trigger for development may be Streptococcus mitis [41], which is the most likely species for translocation across epithelial barriers in the development of neutropenia and infectious complications [57]. However, in most cases, cultures of removed jaw fragments are sterile [20, 41].

Currently, the genetic theory is predominant [2, 52]. Impaired gene expression of IL-10 followed by disruption of the anti-inflammatory balance can explain part of the clinical picture of primary chronic osteomyelitis [2, 52, 60]. An association with autoimmune disorders such as chronic inflammatory bowel disease, Crohn's disease, or arteritis has been described [30]. Inflammatory skin manifestations occur in 23-80% of cases: psoriasis, palmoplantar pustulosis, pyoderma gangrenosum [5]. About 50% of first- or second-degree relatives of individuals with chronic osteomyelitis also have one of these related conditions, most commonly psoriasis or inflammatory bowel disease [11, 22, 54], indicating a genetic component and disease susceptibility. However, various autoimmune diseases are considered associated with skin lesions and may not be included in the diagnosis.

Secondary chronic osteomyelitis of the jaw is associated with the inoculation of microorganisms into the jaw as a result of trauma or odontogenic infection, most commonly of dental origin (pulpal disease, tooth extraction, or foreign bodies) [13]. Other causes, such as steroids, chemotherapeutic agents, and bisphosphonates, may also be associated with this form of osteomyelitis. Odontogenic microorganisms such as S. aureus, S. epidermidis, and Actinomyces typically contribute to the pathogenesis of jaw osteomyelitis, with non-spore-forming anaerobes accounting for 65–75% of the microflora [20].

Productive periostitis. Common causes of periosteal reaction include caries of the molars with concomitant periapical lesions and secondary periodontal infection, fractures, and non-odontogenic infections [56, 49]. Most often, the lesion is located in the area of the 1st molar; less frequently, proliferative periostitis occurs due to caries of the third molar [41]. Periostitis develops as a complication of chronic periodontitis in 74.6% of cases, alveolitis in 14.1% of cases, pericoronitis complications in 6.3%, abscessing periodontitis in 3.5%, and suppurating jaw cysts in 1.7% of cases [80]. Obligate microorganisms such as staphylococci and streptococci predominantly act as infectious agents as a cause of periapical odontogenic infection, although the formation of proliferating periostitis is a relatively rare odontogenic complication [4, 65]. The inflammatory process develops against the background of a low-virulence infection combined with the activation of osteoblastic processes caused by the mixed dentition and active osteogenesis.

Rarefying or post-traumatic periostitis occurs as a consequence of chronic trauma and is most frequently observed in the anterior region of the mandible.

The pathogenesis of primary chronic osteomyelitis remains unclear. The hypothesis of an infectious nature has not been confirmed by multiple microbiological analyses and the ineffectiveness of systemic antibacterial therapy. There are several theories regarding the onset of the disease, but none of them can adequately explain the clinical manifestations. The pathophysiology of PCO development is viewed as an imbalance between pro-inflammatory and anti-inflammatory cytokines affecting cellular and receptor-specific induction of cytokines and chemokines [25, 28]. Pro-inflammatory cytokines such as IL-6 and TNF-α, as well as anti-inflammatory IL-10 [25, 29] and IL-1β [55], play an important role in the pathogenesis of the disease. Inflammatory bone changes under these immunological alterations lead to accelerated differentiation, osteoclast activation, accelerated remodeling, and inflammation due to enhanced interaction between the receptor activator of nuclear factor-κB (RANK) and its soluble ligand RANKL on osteoclast precursor cells [46, 48]. Another pathophysiological trigger is the link between the altered skin microbiome and aseptic bone inflammation, since severe cystic acne and primary chronic osteomyelitis share imbalanced expression and secretion of pro-inflammatory and anti-inflammatory cytokines [46, 53].

In the pathogenesis of secondary odontogenic osteomyelitis, a decisive role is played by errors in the treatment of acute osteomyelitis and disorders of the immune balance, which is based on the sensitization of the body by multiple and chronic foci of odontogenic infection—intensified during exacerbations—and a decrease in the general reactivity of the body. The basis of productive inflammation is the cell-mediated type of immune response (type IV allergy phenomenon), the outcome of which is the formation of granulomatous inflammation and connective tissue, i.e., proliferating areas that subsequently calcify in an attempt to limit the focus of inflammation. Increased vascular permeability, occurring as a consequence of the activation of cells participating in allergic reactions (mast cells, basophils, macrophages, etc.) and their release of a huge amount of allergy and inflammation mediators, leads to impaired blood clotting and fibrinolytic activity, the formation of microthrombi in the bone marrow vessels, and their purulent melting. The nutritional canals of the osteon undergo purulent melting, the affected bone area dies, and a zone of necrosis forms without demarcation inflammation. The accumulation of pus in the bone marrow spaces leads to intraosseous hypertension and the involvement of extraosseous vessels. Collateral edema of the periosteum develops, along with its purulent melting and the release of pus into the surrounding soft tissues of the jaw with the formation of odontogenic phlegmons. The increase in the volume of damage and bone necrosis in osteomyelitis is promoted by secondary mechanisms such as circulatory disorders in the focus and increased hypoxia as a result of venous congestion and lymphostasis; damage to the extraosseous vessel system during periosteal detachment due to exudation, or during drainage of the focus, particularly in the mandible. General predisposing factors for the development of osteomyelitis include: anatomical and topographical features of the structure and blood supply of the bone segment, a decrease in general nonspecific and immune resistance, and background general somatic conditions.

The development of productive periostitis requires a combination of factors [65]:

• presence of a periosteum with high osteoblastic activity

• chronic invasive infection stimulating the formation of new periosteal bone tissue, but insufficiently pathogenic to cause resorption.

• a balance between the host's resistance and microbial virulence so that a mild chronic infection can persist for a sufficiently long time.

Periosteal hyperplasia can also be triggered by the tooth eruption zone, which may be related to the mean age of onset of 8.8–11 years [49]. Inflammatory signals can regulate the periosteal response via matrix metalloproteinase-9 (MMP9) expressed by neutrophils and macrophages in the inflammation zone. MMP9 indirectly affects skeletal cell differentiation by regulating the inflammatory response and the distribution of inflammatory cells, leading to local regulation of cell differentiation in the periosteal region [63]. A critical regulator of inflammation is COX-2, an isoform of cyclooxygenase, the rate-limiting enzyme in prostaglandin biosynthesis. Overexpression of Cox-2 increases the rate of osteogenesis [68]. Excessive inflammatory stimulation by this factor against the background of low-virulence chronic flora, which does not lead to an excessive inflammatory reaction, as well as the period of molar eruption, increases the osteoblastic activity of the periosteum [43].

1.3 Epidemiology of the Disease or Condition

Epidemiological data are scarce; according to literature, the prevalence of chronic non-suppurative forms of osteomyelitis is 1–2 per 1,000,000 [13, 3, 45] or 2–5% of all osteomyelitis cases, although the true prevalence and incidence may be higher [15, 53]. The incidence of secondary osteomyelitis is unknown, as it is a consequence of improper treatment of acute osteomyelitis or the presence of foreign bodies, and it occurs more frequently than primary forms [19].

Chronic jaw osteomyelitis is observed in children of both sexes with a predominant involvement of the mandible [1, 31]. Primary chronic osteomyelitis affects females four times more often than males, and the mean age of onset is 9–10.8 years [5]. Productive forms of periostitis, conversely, are characteristic of males with a male-to-female ratio of 1–1.4:1 and an onset at 8.8–11 years [4].

1.4 Features of Coding the Disease or Condition

K10.2 Inflammatory conditions of jaws

M86 Osteomyelitis

This code includes the following conditions:

1. M86.0 Acute hematogenous osteomyelitis

2. M86.1 Other forms of acute osteomyelitis

3. M86.2 Subacute osteomyelitis

4. M86.3 Chronic multifocal osteomyelitis

5. M86.4 Chronic osteomyelitis with draining sinus

6. M86.5 Other chronic hematogenous osteomyelitis

7. M86.6 Other chronic osteomyelitis

8. M86.7 Other osteomyelitis

9. M86.9 Osteomyelitis, unspecified

1.5 Classification of the disease or condition

A literature review on jaw osteomyelitis reveals a wide range of proposed classifications based on various aspects such as clinical course, radiological features, pathogenesis, and etiology. In most cases, jaw osteomyelitis includes the following conditions:

1. Jaw osteitis (acute/chronic/suppurative)

2. Jaw osteomyelitis (neonatal) (acute/chronic/suppurative)

3. Jaw osteonecrosis (medication-related/radiation-induced) (acute/chronic/suppurative)

4. Jaw periostitis (acute/chronic/suppurative)

5. Bone sequestrum

Most authors classify osteomyelitis into acute and chronic. Acute osteomyelitis differs from chronic osteomyelitis by a duration of less than four weeks from the onset of clinical symptoms. Many authors state that chronic jaw osteomyelitis can be further divided into two main categories: suppurative and non-suppurative [30]. Classifications of chronic osteomyelitis can be divided into the following categories.

By clinical course:

1. Primary chronic

1.1. Juvenile (productive)

1.2. Syndrome-associated:

1.2.1. Chronic recurrent multifocal osteomyelitis / SAPHO syndrome

1.2.2. Majeed syndrome

1.2.3. Deficiency of interleukin-1 receptor antagonist (DIRA)

1.2.4. Pyogenic arthritis, pyoderma gangrenosum, and acne (PAPA)

2. Secondary chronic

2.1. Odontogenic

2.2. Non-odontogenic

2.2.1. Neonatal (hematogenous, metastatic)

2.2.2. Traumatic

2.2.3. Foreign body-induced

2.2.4. Vascular malformation-induced

3. Productive periostitis

3.1. Simple (regressive)

3.2. Ossifying (formerly called Garré's osteomyelitis)

3.3. Post-traumatic

By etiology:

1. Suppurative

1.1. Specific

1.1.1. Tuberculous

1.1.2. Actinomycotic

1.2. Nonspecific

1.2.1. Bacterial

1.2.2. Fungal

2. Non-suppurative

2.1. Osteoradionecrosis

2.2. Medication-related

2.3. Autoimmune

By localization and extent of the infectious-inflammatory process:

1. Maxillary

1.1. Localized (dentoalveolar segment, alveolar part of the jaw; body, ramus of the mandible)

1.2. Widespread (total and subtotal)

2. Mandible

2.1. Localized (dentoalveolar segment, alveolar part of the jaw; body and ramus of the mandible)

2.2. Widespread (total and subtotal)

1.6 Clinical presentation of the disease or condition

Primary chronic osteomyelitis is characterized by a relapsing course with periods of remission and spontaneous exacerbation [15, 36, 24, 53]. Exacerbation episodes last from several days to several weeks with remission periods ranging from several months to several years [60]. Spontaneous remission occurs extremely rarely and lasts from 1 year to 20 years. The disease activity averages 5.5 years (ranging from 0.5 to 19 years); however, some patients do not respond to treatment, and the disease persists into adulthood [53].

Primary chronic osteomyelitis (PCO) can present either monofocally or multifocally [38]. Affected sites include the metaphysis of long bones, pelvis, clavicle, and mandible [27]. However, involvement of the mandible accounts for only 5–18% of all forms of non-bacterial osteomyelitis [5]. Symptoms tend to be more intense the younger the patient is and the earlier the disease onset. Jaw lesions are more common in girls, are typically unifocal, and have an average onset age of 10 years (range 4–14 years). The onset of the disease may occur without predisposing factors such as caries, trauma, radiation, or exposure to chemical agents [61].

Clinical manifestations include bone pain, arthritis, local swelling, and fever, and less commonly skin hyperemia caused by peri-implant or paraosseous inflammation [38]. Systemic manifestations are mild, often limited to low-grade fever, malaise, lymphadenopathy, or growth retardation. High fever or pathological fractures of the affected area are described only in severe cases [24]. In such instances, malignant neoplasms—primarily acute lymphoblastic leukemia and enterocolitis—should be ruled out [44].

When the clavicle, sternum, or jaw is involved, asymptomatic skeletal foci may be present, which is why multifocal involvement should always be suspected [51]. However, PCO can also be a monofocal manifestation of chronic recurrent multifocal osteomyelitis (CRMO) and SAPHO syndrome [1]. Skin diseases (psoriasis, palmoplantar pustulosis, acne, pyoderma gangrenosum, and Sweet's syndrome) and bowel diseases (Crohn's disease, ulcerative colitis, celiac disease) are observed in 25% of individuals [8]. Renal involvement occurs in 10% of patients [64].

Symptoms of mandibular involvement include restricted mouth opening, pain, swelling, regional lymphadenopathy, and paresthesia over the affected area and/or lower lip [1]. Pain often worsens at night and may occur with or without fever [3, 32, 53, 64]. The absence of pus, fistulae, or sequestra in PCO differentiates it from acute and secondary chronic osteomyelitis.

Secondary chronic osteomyelitis

Clinical manifestations of secondary chronic osteomyelitis are associated with the body's reaction to an infectious agent or foreign body and are characterized by the presence of pus, a fistula, and a sequestrum [30].

Productive periostitis

It is characterized by unilateral involvement of the posterior two-thirds of the mandible [67]. The swelling causes moderate facial asymmetry and is asymptomatic and painless. However, there may be a history of pain caused by an odontogenic infection prior to the appearance of swelling in the mandible [37, 67]. With the onset of chronic infection beneath the periosteum, new bone formation begins, and the swelling becomes firmer. From this point on, palpation reveals a bony consistency without active signs of inflammation on the skin and mucosa. Although the volume of bone formation varies, the swelling is always convex in shape. The size can range from 2 cm to involving the entire mandibular body on the affected side, and the thickness of the bony outgrowth can reach 2–3 cm [37]. Despite the non-purulent nature of the new bone formation, skin fistulae occasionally develop, and lymphadenopathy and leukocytosis may also be present [37, 65].

Eversole L. summarized the key manifestations [17]:

• facial asymmetry caused by local bone thickening

• histopathological findings confirming benign periosteal fibrous lesion

• a lesion resulting from infection, trauma, or other irritants

• the ability to completely or partially reshape the bone after removal of the fibrous overgrowth.

2. Diagnostics, medical indications and contraindications for diagnostic methods

Criteria for diagnosing primary chronic osteomyelitis:

Diagnosis requires 2 major or 1 major and 3 minor criteria

2.1 Complaints and Anamnesis

Taking a patient's history is an essential part of clinical examination. Complaints are divided into primary (related to the underlying disease) and secondary [64].

Comments: first of all, the physician needs to establish the relationship between the onset of the jaw inflammatory process and preceding or concomitant reactions to plan comprehensive treatment for inflammatory jaw diseases. To this end, the physician should ascertain: whether the inflammatory process was preceded by dental disease (toothache) or tooth extraction; whether the patient experienced hypothermia, a cold, or physical or emotional stress; what the patient attributes the onset of the disease to; the dynamics of the clinical picture and treatments administered or lack thereof; and evaluate the subjective effectiveness of treatment received during the pre-hospital period [73, 80].

In primary chronic osteomyelitis of the jaw, patients may complain of mild, intermittent pain in the area of the "causative" tooth or jaw, and slight tooth mobility in the inflammation focus. Facial deformity due to jaw thickening may be observed [24].

2.2 Physical Examination

Comments: in primary chronic osteomyelitis, systemic manifestations are generally mild and include low-grade fever, malaise, or growth retardation.

In secondary chronic osteomyelitis, visual examination of oral pathology, including the maxillofacial region, oral cavity inspection using auxiliary instruments (including examination of carious cavities with a dental probe, periodontal pockets with a periodontal probe, determining the degree of mouth opening and restriction of mandibular mobility), percussion in oral pathology, and palpation of the maxillofacial region, joints, and oral organs reveal a relapsing course with periodic exacerbations, abscess formation, and fistula tract development. (The patient's general condition is satisfactory. Body temperature most often returns to normal, though in some patients it periodically rises to 37.3–37.5°C over a long period [73]).

In productive chronic periostitis, the general condition is not impaired [37, 44].

Comments: Examination of patients with chronic jaw osteomyelitis reveals facial asymmetry resulting from minor infiltration of the surrounding soft tissues and periosteal thickening of the jaw. The skin over the thickened bone is normal in color.

Primary chronic osteomyelitis of the mandible presents with restricted mouth opening, edema, and regional lymphadenopathy, and less commonly with paresthesia over the affected area and/or lower lip [1]. Fistulae, pus, or sequestra do not form.

Secondary chronic osteomyelitis may involve the formation of fistulous tracts extending to the bone, from which pus discharges or exuberant bleeding granulations protrude. A number of fistulae undergo scarring and retraction. Lymph nodes decrease in size, become firm, and are less painful on palpation. When the angle and ramus of the mandible are involved, mouth opening is restricted. Inside the oral cavity, the mucosa covering the alveolar process and the body of the jaw is loose, hyperemic or cyanotic, and often thickened. Tooth mobility in the area of the affected bone is increased. Exacerbations are characterized by a worsening of general condition and well-being, and elevated body temperature. In some cases, pus retention leads to the opening of a fistulous tract through which exudate discharges outward, while in others, an abscess or phlegmon develops [71, 73].

Chronic productive periostitis is characterized by the absence of clearly defined clinical symptoms. On external examination, facial asymmetry is either absent or negligible. Palpation reveals a firm, painless thickening of the bone, most often on the vestibular surface. Changes in the oral cavity are minor or absent: purplish-cyanotic mucous membrane; the vascular pattern of the oral vestibule may be pronounced. A skin fistula and regional lymphadenopathy may be present, but these are incidental findings [37, 65].

Comments: A biopsy makes it possible to clarify not only the localization of the focus, but also the nature of the inflammatory process (sterile, purulent), which may be important when deciding on the nature and scope of surgical intervention [71, 80]. In addition, at the initial stages of development, the clinical manifestations of sarcomas are difficult to distinguish from chronic osteomyelitis.

2.3 Laboratory Diagnostics

Comments: To objectively assess the severity of the inflammatory response, clarify the nature of the inflammatory process, and determine the prognosis of the disease, the results of clinical blood tests are important. Their parameters show great diversity, but the most significant among them in the hemogram are the leukocyte differential, erythrocyte counts, and hemoglobin level. These data are especially important in case of a mismatch between the severity of the general and local clinical presentation of inflammatory jaw diseases, in the event of complications, and for assessing the dynamics of patient treatment.

Patients with an exacerbation of secondary chronic jaw osteomyelitis show an increase in the leukocyte count to over 10.0×10⁹/L depending on the type of immunological response, with an increase in neutrophil count (up to 70–80%, including band forms up to 15–20%); the ESR gradually increases up to 40 mm/h in hyperergy or remains at or below normal values in hypoergy. During the resolution stage, hemoglobin and erythrocyte levels normalize, and the counts of leukocytes, including neutrophils, and ESR decrease significantly.

In sluggish osteomyelitis of the jaw, especially in debilitated patients, hemoglobin and erythrocyte levels decrease, the leukocyte count remains low, ESR is within the normal range or reduced, and urinalysis changes persist. During the convalescence stage, parameters gradually recover, while an elevated ESR and a left shift in the leukocyte differential persist [71, 82].

Patients with chronic forms of jaw osteomyelitis exhibit a moderate increase in leukocyte counts and inflammatory markers (serum C-reactive protein) [1,31,32,51]. However, these changes are nonspecific and are elevated in only half of the patients, including during periods of remission [32, 66].

Comments: following a diagnostic biopsy or abscess incision, the material must be sent for bacteriological examination to determine the types of microbial pathogens, their properties, concentration levels, and the susceptibility of infectious agents to systemic antimicrobial therapy [71, 75]. The most common bacteria associated with osteomyelitis are Staphylococcus aureus, Gram-negative bacteria (Pseudomonas aeruginosa), and anaerobic bacteria (Bacteroides fragilis) [6].

2.4 Instrumental Diagnostics

Comments: as part of a comprehensive examination, an X-ray examination should be performed to clarify the localization of inflammation and the potential source, differentiate the inflammatory process of the jaws from a tumor, and, in cases of long-standing disease, determine the extent of bone tissue involvement.

Chronic osteomyelitis manifests with a diverse radiological picture. In primary chronic osteomyelitis, changes may be absent or minimal in the early stages. Early signs of mandibular involvement include diffuse and extensive resorption of cortical and trabecular bone with disruption of the cortical layer. In late stages, a mixed pattern of sclerotic changes and milder osteolytic lesions is observed, and periosteal reactions can occur at any stage [32]. Sequestra are extremely rare [53].

In secondary chronic osteomyelitis, areas of destruction predominate, in the center of which sequestra of various sizes are identified during the substage. Areas of osteosclerosis with a density exceeding that of normal bone tissue are found between them. With the formation of cortical sequestra, the contour of the jaw edge becomes uneven and deformed. Demarcation of sequestra and completion of the sequestral capsule formation occur approximately at 4–6 weeks in the maxilla and at 6–8 weeks in the mandible (in the subacute stage). X-ray diagnosis of a sequestrum is based on identifying an area of intense bone sclerosis surrounded on all sides by a radiolucent zone. At the same level along the bone surface, massive periosteal layers are detected, enclosing the dead piece of bone on all sides. The severity and density of periosteal layers depend on the duration of the process [73, 76].

In chronic productive periostitis, the radiographic presentation of chronic jaw periostitis is fairly typical. At the onset of the disease, an additional shadow of the fibro-thickened or ossified periosteum is detected along the lower border of the jaw, beneath which, as the disease progresses, signs of marginal bone thickening appear. As it remodels, it acquires a pronounced trabecular structure. The primary odontogenic focus is identified [67, 68].

Rarefying periostitis is characterized by a focus of superficial resorption and osteoporosis of the bone tissue with fairly well-defined borders. The bone tissue is replaced by fibrous tissue. Teeth adjacent to the pathological focus are intact [71, 73, 80].

Comments: Computed tomography (CT) is used in a comprehensive examination to detail the process, making it possible to establish the focus of inflammation and determine changes in bone tissue; single-photon emission computed tomography has the highest sensitivity for identifying lesion zones [83]. Computed tomography of the maxillofacial region provides a clear image of the cortical layer, evaluates the condition of surrounding soft tissues, determines the presence of sequestra and periosteal layering, and visualizes osteolysis of the cortical layer and bone trabeculae in detail. This technique is much more sensitive to these changes and allows for the visualization of less pronounced alterations than conventional radiography, as well as three-dimensional reconstruction for surgical treatment planning [71,73]. A typical picture of jaw osteomyelitis includes bone thickening with a strong periosteal reaction, along with osteolytic or sclerotic bone areas [6]. The cortical bone is usually intact and thickened, but there are reports of a cortical defect mimicking a mass. Involvement of the mandible is often associated with widening of the mandibular canal [61]. The germs of the third molar frequently exhibit developmental disorders, likely due to the inflammatory process in the mandible. In all described cases, the appearance of bone-within-bone on CT is a characteristic feature of this disease in children [45]. In the diagnosis of productive periostitis, a characteristic feature is the "dissolution" of the affected zone during the shift in bone density zones, which distinguishes it from other forms of chronic osteomyelitis [41]. The proliferative bone forms layers of radiopaque "onion-skin" lamination. Most proliferative periostitides occur over the compact bone in the area of the involved tooth [37, 65, 67]. Maxillary involvement is rare; however, a case with simultaneous involvement of all four molar regions has been described [65].

Comments: Ultrasound allows for the early detection of edema and infiltrative changes in muscles, as well as fluid collections in tissues. Ultrasound is successfully used for the differential diagnosis of osteomyelitis from soft tissue abscesses, infectious arthritis, and malignant bone tumors in pediatric patients [75, 84].

2.5 Other Procedures

Comments: to clarify the diagnosis and perform differential diagnosis with specific inflammatory diseases and neoplasms of the maxillofacial region, it is necessary to carry out a morphological examination of tissues obtained during surgery (biopsy specimen) [71, 75].

3. Treatment, including drug and non-drug therapies, diet therapy, and pain management

The main components of treatment for patients with inflammatory jaw diseases include:

1. Etiotropic treatment:

   • Surgical treatment (sanation of the lesion zone, including removal of the causal tooth, opening and draining of an oral cavity abscess, focus of soft tissue inflammation of the face or floor of the mouth);

   • Systemic antimicrobial therapy (general and local treatment);

2. Pathogenetic treatment (targeting various links in the pathogenesis of inflammation) – general and local treatment;

3. Symptomatic treatment (elimination of disease symptoms).

Conservative therapy for patients with inflammatory jaw diseases is largely aimed at suppressing the etiological factor, relieving intoxication, and correcting the body's immunological reactivity.

Treatment goals:

elimination of the source of inflammation (removal of the cause of the disease, including opening the purulent focus, if present).

prevention and treatment of complications.

Treatment of inflammatory jaw diseases must be comprehensive and have a pathogenetically substantiated basis that takes into account the patient's age, disease duration, presence of comorbid pathology, functional state of all organs and systems of the body, as well as the stage, form, and prevalence of the inflammatory process in the bone tissue.

The treatment regimen for primary chronic osteomyelitis is divided into two lines [61].

First-line therapy:

• dental prophylaxis and oral sanation

• nonsteroidal anti-inflammatory drugs (M01A)

Second-line therapy:

• planing resection of the lesion zone

• systemic antimicrobial therapy (J01B)

• systemic corticosteroids (H02A) / bisphosphonates (M05BA) / tumor necrosis factor-alpha (TNF-alpha) inhibitors (L04AB) / interleukin inhibitors (L04AC) [61,85] (Appendix B4).

Conservative treatment

Comments: An accurate microbiological diagnosis is the cornerstone in the treatment of osteomyelitis. One of the most important principles of antibiotic therapy is its administration according to strict indications after establishing an accurate diagnosis and identifying the etiological factor of the disease. Stereotyped, routine use of systemic antibacterial drugs is completely unacceptable.

When choosing the drug, dosage, frequency, route of administration, and duration of therapy, it is necessary to consider the following data: weight, age, severity and localization of the inflammatory process, presence of chronic foci of infection and immunodeficient states, and diseases of organs and systems

In primary chronic osteomyelitis, a slight increase in C-reactive protein and sedimentation rate indicates that the condition is an aseptic inflammation. Attempts to perform complex analyses to reveal signs of microbial etiology in primary chronic osteomyelitis are unsuccessful [20, 22]. Reports of various bacterial pathogens obtained during surgery are associated with contamination [20, 22]. There is no data in the literature regarding other microbiological pathogens, particularly fungi or viruses [42]. All of this accounts for the ineffectiveness of systemic antimicrobial therapy [20].

In secondary chronic osteomyelitis, the most frequent bacteria associated with osteomyelitis are Staphylococcus aureus, Gram-negative bacteria (Pseudomonas aeruginosa), and anaerobic bacteria (Bacteroides fragilis) [6]. Rational antibiotic therapy is carried out only after identifying the causative agent and determining its susceptibility based on antibiogram data, knowledge of the pharmacodynamics and pharmacokinetics of the drug, and the clinical presentation of the disease. In case of exacerbation of chronic osteomyelitis, antibiotic therapy is initiated within the first hours of admission to the maxillofacial inpatient unit, even before receiving the antibiogram results. Broad-spectrum antibiotics are prescribed empirically. After determining the species and susceptibility of the given strain, the final correction of systemic antimicrobial therapy is performed. The effectiveness of such therapy should be evaluated 2–3 days after prescribing the drug, with mandatory dynamic microbiological monitoring. It is mandatory to obtain wound discharge and a bone biopsy to determine the susceptibility of microorganisms to systemic antimicrobial chemotherapeutic agents (code J01), antiseptic, and disinfectant agents (D08A) in order to monitor and adjust the ongoing treatment [20]. After receiving the results of the microbiological study, the patient is switched to targeted systemic antimicrobial therapy until a sustained positive trend in the patient's general condition is achieved, the purulent wound is cleansed, and the main symptoms of infection and intoxication disappear.

Comments:

Due to the absence of pathognomonic signs of bacterial infection, absolute criteria for discontinuing systemic antimicrobial therapy do not exist; the decision is made individually based on a comprehensive assessment of the dynamics of the patient's condition and the course of the purulent-inflammatory process. The general criteria for the sufficiency of systemic antimicrobial therapy are as follows:

1) sustained normalization of body temperature;

2) positive dynamics of the main symptoms of infection;

3) absence of signs of systemic inflammatory response;

4) normalization of blood leukocyte count, differential white blood cell count, ESR, and CRP (procalcitonin level if necessary);

5) negative blood culture;

6) normalization of gastrointestinal function.

The persistence of only a single sign of bacterial infection (fever or leukocytosis), as well as the presence of a granulating wound, is not an absolute indication for continuing systemic antimicrobial therapy. The average typical duration of systemic antimicrobial therapy for purulent-inflammatory processes ranges from 5 to 10 days. Prolonging antibiotic therapy may lead to potential complications, increased microbial resistance, and superinfection [78].

Comments: If there is no persistent clinical and laboratory response to adequate systemic antimicrobial therapy within 1–3 days, additional diagnostic examinations (ultrasound of the soft tissues of the maxillofacial region, computed tomography of the maxillofacial region, etc.) are required to detect complications or the formation of a secondary focus of infection in another location (spread of the purulent-inflammatory process and/or formation of fascial spaces/pockets), along with microbiological (culture) examination of wound discharge for aerobic and facultatively anaerobic microorganisms, serial microbiological (culture) blood tests for sterility to determine the species composition of the microbiota, determination of the susceptibility of microorganisms to systemic antimicrobial chemotherapeutic drugs, antiseptics, and disinfectants (D08A), and testing body fluids (blood, urine) for sterility. Based on the results of the additional examination, the ongoing systemic antimicrobial therapy regimen is adjusted, and the purulent-necrotic focus is revised if detected [81].

Comments: in children with a burdened general somatic status, if microbiological cultures yield S. aureus or P. aeruginosa (in mechanically ventilated patients), or in the presence of bacteremia, systemic antibacterial therapy (J01) for at least 14 days is required. Furthermore, prolongation of systemic antibacterial therapy (J01) is indicated in the presence of inflammatory processes in "hard-to-reach" loci (heart valves, central nervous system, bones, prostate gland),

persistence of neutropenia, impossibility of simultaneous surgical debridement and drainage of primary/secondary foci of infection, and inflammation caused by multi- and pan-resistant microorganisms (to achieve their eradication from an epidemiological standpoint).

Upon stabilization of the general condition, transition of the local purulent inflammatory process to phase II, positive dynamics, or normalization of laboratory parameters, systemic antibacterial drugs (J01) are discontinued, and the focus of further treatment is shifted to local effects on the microbiota using antiseptics and disinfectants (D08A) [86].

Comments: Active detoxification of the body is most often carried out in the form of infusion therapy. The main objectives of infusion therapy in patients with inflammatory processes are: elimination of hypovolemia, improvement of microcirculation, restoration of adequate tissue perfusion, normalization of cellular metabolism, correction of homeostasis disorders and blood rheological properties, and reduction of the concentration of inflammatory mediators and endotoxins in the blood.

For infusion therapy as part of targeted intensive care of inflammatory processes in the maxillofacial region, solutions affecting water-electrolyte balance (B05BB) are used. The composition of infusion therapy should be determined by the following factors: patient age, comorbid conditions, prevalence of the process, severity of the disease, and degree of endogenous intoxication. It is necessary to consider the degree of hypovolemia, presence of consumption coagulopathy, nature of changes in biochemical parameters and blood acid-base balance characterizing the specific clinical situation, and the compatibility of the drug's physicochemical properties with it. Controlled hemodilution should be a component of detoxification therapy. The use of balanced solutions for correcting fluid and electrolyte loss is currently well-founded. Balanced solutions include: Compound sodium chloride solution [Potassium chloride + Calcium chloride + Sodium chloride]**, Potassium acetate + Calcium acetate + Magnesium acetate + Sodium acetate + Sodium chloride** [87].

Comments: Hyperbaric oxygen therapy exerts antibacterial, anti-acidotic, and reparative effects on the course of purulent-inflammatory processes in the maxillofacial region [73]. Higher levels of available oxygen induce capillary formation and increase leukocyte activity [18]. Hyperbaric oxygen therapy also stimulates the release of growth factors and stem cells that promote healing [18]. However, this type of treatment is associated with a high relapse rate and the development of potentially life-threatening complications [18, 34]. Moreover, this method can only be used as an adjunct to primary therapy [61].

Comments: Non-steroidal anti-inflammatory and anti-rheumatic drugs (M01A) reduce pain in 40–80% of children [14,21,58,61]. Cyclooxygenase inhibition is activated by NSAIDs for the conversion of arachidonic acid into prostaglandins, which is an important part of osteoclast activation in the jaw, and suppresses excessive bone tissue proliferation. Drugs from the group of other analgesics and antipyretics (N02B) are prescribed: #Metamizole sodium**, paracetamol, salicylic acid and its derivatives (N02BA), ibuprofen**#, #ketoprofen** [27,88].

Comments: Systemic corticosteroids (H02A) in the treatment of primary chronic osteomyelitis are recommended as an intermediate step between the failure of NSAIDs and the initiation of other therapy, as well as for recurrent or severe courses [61]. Oral glucocorticoid intake is recommended at 2 mg of #prednisolone**/kg/day for 1 week with a gradual dose reduction of 25% every 5 days [89]. In cases of persistently recurrent courses, intravenous formulations may be used.

Surgical treatment

Surgical treatment is the main method for inflammatory jaw diseases, consisting of debridement of the inflammatory focus, removal of the cause of the disease (tooth, foreign body), and local drug therapy.

When patients with inflammatory jaw diseases seek medical care, surgical intervention must be performed within a timeframe depending on the severity of systemic manifestations. It is necessary to consider the stage and clinical development of the inflammatory process, its extent and prevalence, and individual patient characteristics (age, presence of comorbidities, etc.).

Principles of treatment of purulent-inflammatory jaw processes:

1) Opening of the purulent focus and removal of the "causative" tooth (if the tooth has not been removed earlier). In case of opening the purulent focus (prior to hospitalization in a specialized hospital), thorough wound revision is performed, and secondary surgical intervention is carried out if necessary,

2) The choice of anesthesia method is decided jointly by the anesthesiologist-resuscitologist and other related specialists (if there is a comorbid pathology) after a thorough examination of the patient, taking into account the indications and contraindications for the type of anesthesia.

Surgical access must correspond to the localization of the inflammation focus. Access to the lesion zone can be performed via external or intraoral access. When choosing surgical treatment, preference should be given to the method in which:

✓ The path to the inflammation focus is the shortest,

✓ During tissue dissection along the path to the focus, the risk of damage to organs and functionally important structures (vessels, nerves) is least likely,

✓ The best conditions are provided for the outflow of exudate, if present, or wound revision, and removal of pathologically altered tissues,

Comments: Surgery is rarely necessary for primary chronic osteomyelitis, but is often performed in patients with jaw lesions before a definitive diagnosis is made [9]. During the operation, it is sufficient to take a small bone fragment, including both cortical and cancellous bone, to rule out any form of bacterial osteomyelitis. However, in severe cases, surgical interventions may be necessary. In addition, although surgical treatment alone cannot guarantee a cure, decortication with the removal of necrotic tissue in the early stages yields a good result, since during the chronic course of inflammation, areas of rarefaction alternate with areas of osteosclerosis [36].

Comments: after elevating the mucoperiosteal flap in the projection of the pathological focus, excision of the proliferatively altered part of the periosteum is performed, and the newly formed bone tissue is removed with bone rongeurs, a chisel, or a bone bur. After removing the excess bone formation, areas of softening may be found on the underlying cortical layer of the bone. The wound is washed with antiseptics and disinfectants, then the flap is repositioned and tightly sutured [70,73,79].

Comments: treatment of an exacerbation of secondary chronic jaw osteomyelitis begins with addressing the presence of comorbid pathology in the patient. In the case of osteomyelitis developing from a multi-rooted tooth, extraction of the tooth is necessary if it cannot be preserved, along with the opening and drainage of the odontogenic abscess, thereby creating better conditions for the outflow of purulent exudate, faster subsidence of acute inflammatory phenomena, and prevention of the further spread of the putrefactive-necrotic process. Tooth extraction must be performed simultaneously with the opening and drainage of purulent foci (phlegmon/abscess) under the periosteum, in the bone, or in the soft tissues. Extraoral surgical access is used in the case of purulent foci in the perimaxillary soft tissues or in the presence of functioning fistulous tracts on the skin [71, 73, 79].

Comments: radical surgical intervention, sequestrectomy, or partial (total) jaw resection is the only correct method of treatment for the secondary chronic form of osteomyelitis. The etiopathogenetic features of the surgical treatment of odontogenic osteomyelitis are: removal of the "causative" tooth, electrical pulp testing of neighboring teeth and those located in the inflammation focus, endodontic treatment of affected teeth in the preoperative period and mobile teeth, and the implementation of instrumental and drug treatment of the root canal using various methods.

Depending on the localization of the sequestrum, intra- and extraoral surgical approaches are used. In the case of an osteomyelitic process in the maxilla, it is rational to use intraoral approaches. When osteomyelitis of the maxilla is complicated by maxillary sinusitis or sequestration of the sinus walls, it is advisable to perform sequestrectomy as a radical maxillary sinus surgery (Caldwell-Luc operation). On the mandible, external incisions are more frequently used; in particular, external surgical access is indicated in the case of subtotal jaw osteomyelitis, as well as in the presence of fistulas at a considerable distance from the affected bone area. In such cases, typical skin incisions are used, respecting the principles of the anatomical arrangement of vessels and nerves and for aesthetic considerations. Surgical intervention consists of a wide opening of the sequestral cavity, removal of the pathological focus, excision of the superficial and deep fistulous tracts, and necrotectomy of non-viable tissues [72]. When performing jaw resection, mechanical processing of the bone tissue is carried out until the appearance of the "red dew" sign, which is an indicator of healthy bone [59].

In rarefying periostitis and hyperplastic forms of chronic osteomyelitis, surgical intervention in the volume of opening and drainage of a phlegmon/abscess in the bone tissue, necrotectomy, and curettage of granulations is indicated.

The issue of the urgency and scope of surgical intervention has a clear justification—it is performed only after the formation of a sequestral cavity and complete demarcation of the sequestrum based on the clinical and radiological picture in secondary chronic osteomyelitis [79].

Comments: optimal drainage ensures a full outflow of wound exudate, creates the best conditions for the rapid rejection of dead tissue and the transition of the process from the inflammation phase to the regeneration phase. The main means used as drainage are the Penrose latex drainage tube or the Endo Drain four-channel silicone drainage.

In the postoperative period, after opening purulent foci and eliminating the primary cause of the disease, an important role in prevention is assigned to local wound management.

Local wound treatment includes drug effects on the purulent wound and complements surgical treatment, depending on the phase of the wound healing process, taking into account all principles of therapy for purulent-inflammatory diseases. In this regard, it is necessary to adhere to a differentiated approach in choosing drugs for the local treatment of purulent wounds.

Inflammation phase—the first phase of the wound healing process. In this phase, combating infection is of great importance, so medications must have antimicrobial, dehydrating, necrolytic, and, if possible, analgesic effects, i.e., contribute to the suppression of microflora and rapid cleansing of the wound, creating conditions for repair.

Comments: daily irrigation, instillation, intraosseous lavage with antiseptic and disinfectant solutions (D08A), antimicrobials and antiseptics for local treatment of oral diseases (A01AB): chlorhexidine solution for topical and outdoor use 0.02% and 0.05%**, benzyldimethylmyristoylamino-propylammonium 0.01% solution, #povidone-iodine solution for topical and outdoor use 10%** diluted 10 or 100 times, 7.5%. Various instrumental methods for purulent wound debridement can be used: laser, plasma, vacuum, ultrasonic cavitation, and wound treatment with a pulsating stream of antiseptic solution. Active local drug therapy should be used in phase I of the wound healing process. It is also recommended to use biguanides and amidines D08AC – chlorhexidine solution for topical and outdoor use 0.05–0.2%**, #hexetidine and quaternary ammonium compounds (D08AJ) – benzyldimethylmyristoylamino-propylammonium, sodium deoxyribonucleate 2.5 mg/ml, solution for topical and outdoor use [75, 94].

The regeneration phase is phase II of the wound healing process, characterized by the formation and maturation of granulation tissue. This period is marked by the appearance of islands of granulation tissue in the wound, which grow to completely cover the wound surface. Healthy granulation tissue is always bright, succulent, and easily bleeds. At the slightest deterioration of biosynthetic processes in the wound, the appearance of granulations changes: they lose their bright color, become small, and are covered with a mucous coating. Any slowdown in the development of granulations leads to a delay and cessation of the epithelialization process. During this period of the wound healing process, drainage is not required.

Comments: in the regeneration phase, it is necessary to use drugs for the treatment of wounds and ulcers D03 and other drugs for topical treatment of oral diseases A01AD, as the fight against infection continues, to improve tissue microcirculation, cellular and tissue metabolism, thereby promoting granulation growth and rapid wound epithelialization. Such drugs include: #solcoseryl dental adhesive paste, #sea buckthorn oil, #dioxomethyltetrahydropyrimidine, #povidone-iodine 10% ointment*, and other drugs for topical treatment of oral diseases A01AD [95].

The scar reorganization and epithelialization phase is phase III of the wound healing process. The main objective of treatment in phase 3 is to stimulate reparative processes and epithelialization.

Comments: in the postoperative period, bisphosphonates (M05BA) may be prescribed to increase osteoinductive activity and prolong the remission period. The effect of bisphosphonate therapy is achieved by suppressing pro-inflammatory cytokines such as TNF-α, IL-6, and IL-1, increasing bone mass and mineralization, which leads to long-term remission [24, 46]. The most studied is #pamidronic acid (LS-002437), usually prescribed at a dose of 1 mg/kg/dose (maximum 60 mg/dose) every month or 1 mg/kg/dose (maximum 60 mg/dose) for 3 consecutive days every 3 months [92].

4. Medical Rehabilitation and Sanatorium-Resort Treatment

Not provided.

5. Prevention and Dispensary Observation

To ensure complete rehabilitation of patients with inflammatory jaw diseases, especially jaw osteomyelitis, a coordinated team of specialists is required: an anesthesiologist-resuscitator, oral surgeon, general dentist, prosthetic dentist, maxillofacial surgeon, pediatrician, physical therapy doctor, and exercise therapy doctor. Rehabilitation measures are carried out based on specific clinical manifestations (dental, neurological, functional, etc.) and are subject to consideration in the relevant clinical guidelines.

Comments: timely and correct prescription of physiotherapeutic procedures in the complex treatment of patients with purulent-inflammatory jaw diseases helps to relieve acute inflammatory events, improves tissue microcirculation, helps to reduce purulent exudate and wound regeneration. Physiotherapeutic treatment can be included in the complex of therapeutic measures after adequately performed surgical intervention, effective wound drainage, a comprehensive examination of the patient, and against the background of drug therapy, necessarily taking into account the phase of the wound healing process. In chronic forms of inflammatory jaw diseases, drug electrophoresis, ultrasound therapy, and paraffin application for bone diseases may be prescribed [75].

Comments: in the acute period of inflammation, it is necessary to perform exercises to strengthen the muscles of the face and neck not associated with damaged tissues; the exercises should be dosed and aimed at improving tissue microcirculation and preventing the formation of rough scars. Exercise therapy in the subacute and chronic stages aims to prevent the development of contractures, restore the mobility of the temporomandibular joint and the functions of various muscle groups, complete scar formation and wound epithelialization, while the appointment of a general health-improving regimen promotes optimal recovery of the body [71].

The basis for the prevention of inflammatory jaw diseases is dental sanation, which consists of a set of measures for the detection and treatment of dental caries and its complications, and inflammatory periodontal diseases.

Comments: in the prevention of dental caries and its complications, as well as periodontal diseases, a major role is assigned to oral hygiene, awareness-raising work, and oral hygiene training. Visits to the general dentist and oral surgeon should be carried out at least once a year, and professional oral hygiene should be performed at least once every 6 months [77].

Indications for preventive measures:

• poor oral hygiene;

• presence of periodontal disease in the patient;

• presence of concomitant pathology in the patient in a decompensated form.

Contraindications to preventive measures: none absolute.

6. Organization of Medical Care

Type of care delivery: medical care (MC) in the profile "maxillofacial surgery":

• Specialized and High-Tech MC.

• Emergency, including specialized emergency MC.

Conditions of medical care delivery: outpatient, inpatient.

7. Additional Information

Additional information (including factors influencing the outcome of the disease)

1. Inadequate opening and drainage of the purulent focus, which can lead to the progression of the inflammatory process and its spread to surrounding tissues.

2. Non-compliance with the local contact hypothermia regimen in the early postoperative period.

3. Non-compliance with oral hygiene.

4. Non-compliance with physiotherapy and physical therapy recommendations in the postoperative period.

5. Lack of follow-up care (dispensary observation)

6. Non-compliance with other recommendations of the attending physician (general and local treatment, diet, etc.).

7. Presence of decompensated forms of somatic diseases in the patient.

Organization of medical care delivery

Indications for emergency hospitalization to a medical organization

1) Exacerbation of chronic osteomyelitis in the presence of concomitant diseases in sub- or decompensated forms in the patient; hyperergic course of the inflammatory process; malignant neoplasms of any localization; conditions accompanied by immunodeficiency of the body,

2) Indications for emergency hospitalization of children of any age: inability to perform surgical treatment using local anesthesia (inadequate child behavior, presence of concomitant pathology or allergy to local anesthetics), absence of a qualified specialist (dental surgeon), hyperergic course of the inflammatory process.

Indications for planned hospitalization in a medical organization:

1. Chronic jaw osteomyelitis in the presence of a formed sequestrum.

2. Chronic jaw osteomyelitis in case of a protracted, torpid, or progressive course of the disease and prolonged formation of sequestra.

Indications for hospital discharge

1) Uncomplicated early postoperative period, satisfactory patient condition, controlled pain syndrome manageable with oral medications, possibility of systemic antimicrobial therapy in an outpatient setting under the supervision of a maxillofacial surgeon, oral surgeon, or general surgeon,

2) Need for transfer of the patient to another medical institution or department,

3) At the request of the patient or their legal representative,

4) In cases of non-compliance by the patient with prescriptions or internal hospital regulations, if this does not threaten the patient's life and the health of others.

Further monitoring and treatment of the patient shall be carried out on an outpatient basis by a maxillofacial surgeon, or in their absence, by an oral surgeon, general surgeon, pediatric dentist, or pediatric surgeon.

Risk of recurrence:

Recurrence not only severely impacts patients' lives but also leads to physiological and psychosocial impairments. Risk factors include the following indicators [12]:

• age from 6 to 12 years, as patients are in the mixed dentition period, which harbors more pathogenic bacteria than deciduous or permanent dentition,

• leukocytosis and fever upon admission, as leukocyte count and temperature positively correlate with infection severity. A leukocyte count exceeding 15×10⁹/L or a temperature exceeding 39 degrees Celsius typically indicates a severe infection, which in itself can be a life-threatening complication,

• MSI infection increases the risk of recurrence fourfold,

• prior antibiotic administration, as prolonged antibiotic abuse leads to drug resistance,

• diabetes, as elevated blood glucose leads to increased glucose content in the body, promoting bacterial growth and reproduction.

Criteria for Evaluating the Quality of Medical Care

References

Appendix A1. Working Group Composition

1. Kulakov A.A. – Academician of the Russian Academy of Sciences, MD, Professor, President of the LLC "Association of Specialists in Maxillofacial Surgery"

2. Lopatin A.V. – Professor, MD, Deputy General Director for Scientific and Clinical Work, Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology of the Russian Ministry of Health

3. Kugushev A.Yu. – MD, Head of the Department of Maxillofacial Surgery, Russian Children's Clinical Hospital

3. Semenov M.G. – Maxillofacial surgeon, MD, Professor, highest category physician

4. Topolnitsky O.Z. – MD, Professor, Honored Physician of the RF, Head of the Department of Pediatric Maxillofacial Surgery, A.I. Evdokimov Moscow State University of Medicine and Dentistry.

All members of the working group are members of the All-Russian Public Organization "Association of Specialists in Maxillofacial Surgery".

Conflict of interest is absent.

Appendix A2. Methodology for Developing Clinical Guidelines

Target audience of these clinical guidelines:

1. maxillofacial surgeon

2. oral surgeon

3. pediatric surgeon

4. pediatric oncologist

5. pediatric dentist

6. students, residents, postgraduate students of medical institutions.

Table 1. Level of Evidence (LoE) rating scale for diagnostic methods (diagnostic interventions)

Table 2.  Scale for assessing levels of evidence (LE) for prevention, treatment, and medical rehabilitation methods, including those based on natural therapeutic factors (preventive, therapeutic, and rehabilitative interventions)

Table 3. Grade of Recommendation (GoR) rating scale for methods of prevention, diagnosis, treatment, and medical rehabilitation, including those based on natural healing factors (preventive, diagnostic, therapeutic, and rehabilitative interventions)

Procedure for updating clinical guidelines

The mechanism for updating clinical guidelines provides for their systematic revision at least once every three years, as well as upon the emergence of new evidence-based medicine data on the diagnosis, treatment, prevention, and rehabilitation of specific diseases, or in the presence of justified additions/comments to previously approved clinical guidelines, but no more frequently than once every 6 months.

Appendix A3. Reference Materials

These clinical guidelines were developed taking into account the following regulatory legal documents:

• Federal Law No. 323-FZ of November 21, 2011 (as amended on December 28, 2024) "The Fundamentals of Healthcare Protection in the Russian Federation" (with rev. and add., effective from March 1, 2025)

• Order of the Ministry of Health of Russia No. 804n dated October 13, 2017 (as amended on September 24, 2020, with rev. dated October 26, 2022) "On Approval of the Nomenclature of Medical Services"

• Order of the Russian Ministry of Health No. 103n dated February 28, 2019 (as amended on September 28, 2023) "On approval of the procedure and timelines for the development of clinical guidelines, their revision, standard template of clinical guidelines and requirements for their structure, composition and scientific validity of information included in clinical guidelines"

• Order of the Russian Ministry of Health No. 422n dated June 14, 2019 "On approval of the Procedure for rendering medical care in the specialty 'maxillofacial surgery'"

• Decree of the Government of the Russian Federation No. 2406-r dated October 12, 2019 (as amended on January 15, 2025) "On approval of the list of vital and essential medicines, as well as lists of medicines for medical use and the minimum assortment of medicines required for medical care"

The development of clinical guidelines took into account the following programs and educational materials:

• AMRControl (Antimicrobial Resistance Control Strategy) Program in inpatient medical care / Russian Clinical Guidelines Moscow – 2018.

• EUCAST European Committee on Antimicrobial Susceptibility Testing http://www.eucast.org

• Materials of the Russian "Sepsis Forum" - "Russian Sepsis Forum".

• Golub I.E. Sepsis: definition, diagnostic concept, pathogenesis, and intensive care: Textbook / I.E. Golub, L.V. Sorokina, E.S. Netesin. – Irkutsk: ISMU, 2015. – 47 p.).

• Management of patients with sepsis and septic shock in a multidisciplinary hospital. Study guide, Moscow Regional Research Clinical Institute named after M.F. Vladimirsky (MONIKI), Moscow, 2015, 35 p.

Appendix B. Physician Action Algorithms

1. Comparison between primary chronic osteomyelitis and suppurative osteomyelitis of the jaws

2. Schematic diagram of primary chronic osteomyelitis treatment

3. Differential diagnosis of primary chronic osteomyelitis

4. Schematic conservative treatment of primary chronic forms of jaw osteomyelitis

Appendix C. Patient Information

Inflammatory jaw diseases, such as periostitis or osteomyelitis, are quite common in dental surgeon practice, whereas chronic forms are rare. The patient should be aware that upon the onset of acute tooth or jaw pain, followed by facial soft tissue swelling and fever, self-treatment is unacceptable, and medical assistance should be sought immediately at a healthcare facility or by calling an ambulance. In case of a protracted acute course or lack of tendency to recovery, hospital examination is necessary, as neoplasms present with a similar clinical picture. Surgical treatment for chronic inflammatory jaw diseases is predominantly surgical, and delayed specialized medical care can lead to severe complications and even death. During exacerbations of primary chronic osteomyelitis, patients complain of bone pain, arthritis, local swelling, and fever. Localized skin redness caused by paraosseous inflammation is a rare symptom. Systemic manifestations are usually mild and include low-grade fever, malaise, or growth retardation [24].

In secondary chronic osteomyelitis, patients may complain of postoperative scars or fistulous tracts (with abundant granulation tissue) with purulent discharge from both the skin and the oral cavity. Probing of the fistulous tract may reveal a mobile area of bone with an uneven surface. The general condition is satisfactory; low-grade fever, bouts of general weakness, malaise, and sweating may occur periodically [73, 80]. During an exacerbation of secondary chronic osteomyelitis, the patient is disturbed by jaw pain and facial soft tissue swelling. When the infectious-inflammatory process spreads to adjacent anatomical structures, complaints characteristic of the inflammatory process in the corresponding localization appear: limitation and painful mouth opening, pain during swallowing, talking, tongue movement, nasal congestion or purulent nasal discharge in the case of sinus empyema. Patients note the gradual onset of tooth mobility in the area of the purulent-inflammatory process, purulent discharge from periodontal pockets or fistulous tracts. Percussion of the tooth group is markedly positive. A «muff-like» infiltrate around the jaw. In addition, there is body-wide pain, significant weakness, loss of appetite, poor sleep, often insomnia, fever, and headaches. Hectic temperature curve. Evening temperature spikes. In lesions of the mandible, a pathognomonic symptom when the process spreads below the level of the mandibular canal is a decrease or loss of sensitivity of the lower lip and chin skin (Vincent's symptom) [73, 80].

In chronic productive periostitis, patients may complain of a unilateral thickening of the jaw in the area of inflammation from both the skin and oral cavity sides [70]. The swelling causes moderate facial asymmetry and is asymptomatic and painless. However, the history may indicate pain caused by an odontogenic infection prior to the appearance of swelling along the lower border in the posterior two-thirds of the mandible [37, 70].

Appendix G. Assessment Scales, Questionnaires, and Other Evaluation Tools

None provided.