Subacute Osteomyelitis (Brodie Abscess) 

Subacute osteomyelitis is a distinct form of osteomyelitis, and Brodie abscess is one type of subacute osteomyelitis. Subacute osteomyelitis is difficult to diagnose because the characteristic signs and symptoms of the acute form of the disease are absent.^{[1, 2, 3]} The disease has an insidious onset, mild symptoms, and lacks a systemic reaction, and supportive laboratory data are inconsistent. Subacute osteomyelitis may mimic various benign and malignant conditions, resulting in delayed diagnosis and treatment. The most frequently made incorrect diagnosis is that of tumor.^{[1, 4, 5]}

In noncontemporary literature, Brodie abscess was referred to as a chronic form of osteomyelitis; however, in almost all contemporary literature references, Brodie abscess is referred to as the most common type of the subacute form of osteomyelitis.

An image depicting subacute osteomyelitis can be seen below.

Sir Benjamin Brodie, a surgeon in St. George's Hospital, London, United Kingdom, first described subacute osteomyelitis in 1832.^[6] He amputated the leg of a man who had intractable pain for a number of years. On examination of the amputated limb, Brodie found a cavity the size of a walnut filled with dark-colored pus. The bone immediately surrounding the cavity was whiter and harder than the surrounding bone. The inner surface of the cavity appeared to be highly vascular.^[6] Since then, low-grade pyogenic abscesses of the bone have frequently been referred to as Brodie abscesses.

In 1951, Wiles referred to Brodie abscesses as a particular form of chronic osteomyelitis that follows an acute attack, when the virulence of the organism and the resistance of the patient are evenly balanced.^[7] Little discussion exists in the literature again until Harris and Kirkaldy-Willis described primary subacute osteomyelitis^[8] ; they were the first to publish a radiograph that demonstrated an abscess of subacute osteomyelitis crossing the epiphyseal plate of the distal tibia. Based on their experience in East Africa, Harris and Kirkaldy-Willis classified primary subacute osteomyelitis, into 2 types, depending on whether a bone abscess is present or not, with the first type being metaphyseal and the second type diaphyseal. Subsequently in 1973, Gledhill proposed a radiologic classification for primary subacute osteomyelitis that consisted of 4 types based on his review of 8 patients, as follows^[9] :

• Type I – Solitary lesion with surrounding sclerosis, classic Brodie abscess
• Type II – Metaphyseal radiolucent lesion with an associated loss of cortical bone
• Type III – Diaphyseal cortical hyperostosis without onion-skinning
• Type IV – Diaphyseal lesions associated with onionskin layering

In 1982, Roberts et al modified and expanded Gledhill's classification to 6 forms based on morphology, location, and similarity to neoplasms, as follows^[10] (see image below):

• Type Ia lesions present as a punched-out radiolucency that is often suggestive of eosinophilic granuloma (see images below). Type Ib lesions are similar to type Ia lesions but have a sclerotic margin and appear as a classic Brodie abscess. Anteroposterior radiograph of the distal radius. This image depicts a central metaphyseal lesion (punched-out radiolucency), type Ia. Lateral radiograph of the distal radius. This image depicts a central metaphyseal lesion (punched-out radiolucency), type Ia.
• Type II lesions erode the metaphyseal cortex and may appear similar to osteogenic sarcoma (see images below). Anteroposterior radiograph of the left tibia. This image depicts periosteal reaction of the diaphyseal cortex, type IIb. Lateral radiograph of the left tibia. This image depicts periosteal reaction of the diaphyseal cortex, type IIb.
• Type III lesions are observed as a localized diaphyseal cortical and periosteal reaction simulating osteoid osteoma (see images below). Anteroposterior and lateral radiographs of the distal femur. These images depict a type IIIa epiphyseal lesion. Lateral radiograph of the left tibia. This image depicts periosteal reaction of the diaphyseal cortex, type IIb. Anteroposterior radiograph of the distal tibia. This image depicts an eccentrically located radiolucent lesion crossing the epiphyseal plate, type IIIb. Lateral radiograph of the distal tibia. This image depicts an eccentrically located radiolucent lesion crossing the epiphyseal plate, type IIIb.
• Type IV diaphyseal lesions most often resemble Ewing sarcoma, with onionskin periosteal reaction (see images below). Lateral radiograph of the lumbosacral spine. This image depicts destruction of bone and disc space, type IVa. Computed tomography scan cut of the right lower extremity. This image depicts a sclerotic lesion of the right iliac bone, type IVb.
• Type V lesions occur in the epiphysis and appear as a concentric radiolucency.
• Type VI lesions involve the vertebral body with an erosive or destructive process.

This classification system is the most widely used in the literature, and several reports advocate modifying the classification system to include flat bone involvement, tarsal bones, and lesions affecting both the metaphysis and the epiphysis. Some authors have modified the Roberts's classification system (see Introduction, Clinical, below). In all reported series of primary subacute osteomyelitis, the classic Brodie abscess (central metaphyseal lesion with well-defined sclerotic margins, type Ia according to the authors' new classification system) has comprised the largest number of cases.

Subacute osteomyelitis is characterized by mild to moderate pain, usually described as a persistent ache; intermittent symptoms; insidious onset; and, often, a long delay between the onset of pain (the most common presenting symptom) and the diagnosis. Usually, symptoms are present for 2 weeks or longer. The course is generally marked by few or no constitutional symptoms and no known previous acute disease.

Frequency

The incidence of subacute osteomyelitis has increased since antibiotics have been used to treat osteomyelitis. The disease reportedly accounts for 8.8%,^[11] 35%,^[12] and 42%^[13] of primary bone infections, although a report by Blyth et al indicates a mild decline in the incidence of both acute and subacute osteomyelitis, with greater decline in the acute form than in the subacute form.^[14] In East Africa, subacute osteomyelitis is the most common form of osteomyelitis.

Onset of subacute osteomyelitis tends to occur in slightly older children than the onset of acute osteomyelitis. Subacute osteomyelitis has been reported in patients as young as 6 months and as old as 39 years, but the common age range is 2-15 years. Sex ratios vary, but in general, males are affected slightly more often than are females.

Subacute osteomyelitis is one of the many clinical presentations of hematogenous osteomyelitis. The organisms reach the bone from a disrupted site elsewhere in the body that may pose little or no threat of its own accord (eg, skin pustule, furuncles, impetigo, infected blisters and burns). Infection has even been suggested to be the outcome of common events such as normally harmless daily teeth brushing.

Factors that may influence the behavior of a septic process in bone may relate to host resistance, virulence of the infecting organism, and adequacy of antibiotic therapy. Moreover, subacute osteomyelitis appears to depend on the interplay between the infecting bacteria and the immune mechanism of the host. True primary subacute osteomyelitis represents a favorable host-pathogen response. In East Africa, where subacute osteomyelitis is the most common form of osteomyelitis, children in bare feet have frequent foot infections and develop a high resistance to staphylococcal infections (the most common causative organism), as pointed out by Harris and Kirkaldy-Willis.^[8]

That trauma results in vascular injury and an area of hypoxia in the metaphyseal region of bone is an attractive theory, but it is difficult to prove as an inciting cause of subacute osteomyelitis. When the host resistance is insufficient to overwhelm the infection, it is conceivable that subacute osteomyelitis may develop.

The pyogenic organisms' initial attack is presumed to be controlled by the host, and presumably, spread to large areas of cancellous tissue or to the subperiosteal region has not occurred. A central area of suppurative necrosis in the metaphyseal region becomes enclosed by a wall of fibrous tissue and granulations, the offending organisms are destroyed, and the pus is usually sterile.

The circulation of the epiphysis predisposes to sluggish blood flow through the vascular loops. Possibly, the rich supply of the reticuloendothelial cells located in the epiphysis attenuates the osteomyelitis, leading to the subacute course in this region.

The metaphyseal-equivalent regions are defined as the portion of a flat or irregular bone that borders cartilage (apophyseal growth plates, articular cartilage, or fibrocartilage), such as the pelvis, the vertebrae, the clavicle, and the small bones (tarsal bones).^[15] The vascular anatomy and the mechanism of seeding are analogous to those found in the metaphysis of long bones.

Site of infection

Subacute osteomyelitis occurs in a much wider variety of bones than does the acute type, and the disease occurs at various sites within the affected bones. The lower limb is affected much more often than the upper limb, and the tibia is affected relatively more often than is the femur.^[16] Subacute osteomyelitis may involve only the epiphysis, which is contrary to the belief that primary bone infection does not occur in the epiphysis (see image below).

The diaphysis is occasionally affected (see first 2 images below), although this occurs more often in adults than in children; the most commonly affected site is the metaphysis (see last 2 images below).

Communication of the lesion between the metaphysis and the epiphysis is also common (see images below).

Other sites in which subacute osteomyelitis is frequently reported are metaphyseal-equivalent locations, such as the pelvis, the vertebrae, the calcaneum, the clavicle, and the talus. When subacute osteomyelitis occurs in tarsal bones, it usually occurs in the subchondral part or on the border of the apophysis of the calcaneus. Subacute lesions of the spine occur more often in adults than in children (see image below).

When subacute osteomyelitis occurs in the long bones of adults, the diaphysis is involved as often as is the metaphysis. The patella is rarely involved. Multifocal subacute osteomyelitis is a rare form of subacute osteomyelitis that was reported by Season and Miller and by Rasool.^{[17, 18]} It is usually associated with a deficient immune system.

Bacteriology

The causative organism is usually coagulase-positive Staphylococcus (30-60%). Other organisms encountered are Streptococcus, Pseudomonas, Haemophilus influenzae (much less common after widespread vaccination), and coagulase-negative Staphylococcus. An increased prevalence of Kingella kingae, a gram-negative coccobacillus, was noted by Lundy and Kehl, mostly in children younger than 3 years as a cause of all types of osteoarticular infections, including subacute osteomyelitis.^[19]

Patients with sickle cell anemia are predisposed to infections with Salmonella, whereas Pseudomonas aeruginosa is isolated from skeletally mature intravenous drug abusers. However, in almost 25-50% of cases of subacute osteomyelitis, no organism is cultured.^[20]

Presenting symptoms of subacute osteomyelitis include mild to moderate localized pain. Pain is the most consistent complaint in most patients, and it may at times become more intense or remit and is frequently exacerbated following a period of unusual activity. Night pain that is relieved with aspirin is frequently reported. Minimal loss of function is another common symptom (eg, limping in a patient with a lower limb lesion), with no history of systemic toxicity.

On clinical examination, localized tenderness may only occasionally be associated with warmth, redness, and soft-tissue swelling with the involvement of subcutaneous bone. This finding seems to increase and subside with activity. Pain may occur with movement of the adjacent joint, and some joint effusion may be present, but the pain and effusion are usually mild. The surrounding muscles may occasionally demonstrate some wasting.

Classification

Ross and Cole categorized these lesions either as aggressive or as cavities in the area of the metaphysis and epiphysis.^[21] This categorization helps in the treatment plan, as aggressive lesions should be treated surgically for diagnosis. Gledhill classified subacute osteomyelitis according to radiologic appearance,^[9] and this classification scheme has since been modified by Roberts et al.^[10] The classification scheme is useful for reporting the results of treatment according to the site but is not a prognosis or treatment plan. The authors have modified the latter as follows (see image below):

• Type I is a metaphyseal lesion.

  • Type Ia is a central metaphyseal lesion that is seen as a punched-out radiolucency, often suggestive of Langerhans cell histiocytosis (see images below). Anteroposterior radiograph of the distal radius. This image depicts a central metaphyseal lesion (punched-out radiolucency), type Ia. Lateral radiograph of the distal radius. This image depicts a central metaphyseal lesion (punched-out radiolucency), type Ia.
  • Type Ib is a metaphyseal lesion eccentrically located with cortical erosion, which may give the appearance of osteogenic sarcoma.
• Type II is a diaphyseal lesion.

  • Type IIa is a localized cortical and periosteal reaction that simulates osteoid osteoma.
  • A type IIb lesion is a medullary abscess in the diaphysis without cortical destruction but with onionskin periosteal reaction that resembles Ewing sarcoma (see image below). Anteroposterior radiograph of the left tibia. This image depicts periosteal reaction of the diaphyseal cortex, type IIb.
• Type III is an epiphyseal lesion.

  • Type IIIa is a primary epiphyseal osteomyelitis and appears as a concentric radiolucency. This type is usually seen in children younger than 4-5 years (see image below). Anteroposterior and lateral radiographs of the distal femur. These images depict a type IIIa epiphyseal lesion.
  • Type IIIb is a subacute infection that crosses the epiphysis and involves both the epiphysis and metaphysis (see images below). Anteroposterior radiograph of the distal tibia. This image depicts an eccentrically located radiolucent lesion crossing the epiphyseal plate, type IIIb. Lateral radiograph of the distal tibia. This image depicts an eccentrically located radiolucent lesion crossing the epiphyseal plate, type IIIb.
• A type IV lesion is a metaphyseal-equivalent lesion, which is defined as the portion of a flat or irregular bone that borders cartilage (apophyseal growth plates, articular cartilage, or fibrocartilage), such as the vertebrae, the pelvis, and small bones (eg, tarsal bones and clavicle).^[15]

  • Type IVa involves the vertebral body with an erosive or destructive process (see image below). Lateral radiograph of the lumbosacral spine. This image depicts destruction of bone and disc space, type IVa.
  • Type IVb involves the flat bones of the pelvis and is mostly sclerotic, with neither erosion nor destructive processes. Ezra et al mentioned this type in 1993 and 1997 (see image below).^{[22, 23]} Computed tomography scan cut of the right lower extremity. This image depicts a sclerotic lesion of the right iliac bone, type IVb.
  • Type IVc involves the small bones (eg, tarsal bones, clavicle).

Duration of symptoms

Because the symptoms of subacute osteomyelitis are vague, an accurate diagnosis is usually delayed. The bone lesion may also not be readily apparent on plain radiographs for some time. The average duration of symptoms before diagnosis is 1-6 months, but symptoms may be present longer before the diagnosis.

Differential diagnosis

Osteomyelitis is a known mimic of various diseases, and subacute osteomyelitis is no exception, having all of the presenting signs and symptoms of many bone tumors, both benign and malignant. The variety of radiographic presentations of subacute osteomyelitis has been emphasized by Gledhill.^[9] The classic solitary lesion located in the metaphysis surrounded by reactive new bone presents little difficulty in diagnosis. However, extensive erosions of cortical bone, periosteal new bone formation, or both may add a more ominous dimension.

Patients with subacute osteomyelitis may occasionally be initially diagnosed with Ewing sarcoma or osteogenic sarcoma. From these observations, the following lesions must be considered among the differential diagnosis of subacute osteomyelitis:

• When the lesion is diaphyseal and associated with an onionskin periosteal reaction, it may be confused with Ewing sarcoma, Langerhans cell histiocytosis, or, much less likely, osteogenic sarcoma.
• When the lesion is epiphyseal, it may be confused with a chondroblastoma, fungal osteomyelitis, or tuberculous osteomyelitis, or with an aneurysmal bone cyst, pigmented villonodular synovitis (PVNS) erosions, giant cell tumor, or gout, depending upon the age of the patient.
• Metaphyseal eccentric lesions may be confused with the more common nonossifying fibroma, although, typically, the diagnosis of nonossifying fibroma is easily made, as is the diagnosis of chondromyxoid fibroma.
• Brodie abscesses, osteoid osteoma, and intracortical hemangioma should all be included in the differential diagnosis of an intracortical bone lesion.

Subacute osteomyelitis treatment is controversial; however, in patients with characteristic clinical and imaging findings and laboratory results, treatment with antibiotics alone may be undertaken without biopsy, at least in the pediatric age group.^{[3, 21, 23, 24, 25, 26, 27]} In the literature, opinion differs as to whether treatment should be surgical or medical for these classic lesions. Failure of symptoms to resolve after an up to 6-week course of antibiotics or worsening of the condition during treatment should lead to reevaluation and a definite tissue and/or bacteriologic diagnosis, followed by surgical treatment and appropriate antibiotics.

Other indications for surgery are impending sinus formation or drainage into a synovial joint. Clinical signs of subperiosteal pus or synovitis indicate that the subacute infection has transformed into an acute component, and it must be drained surgically.

Interconnecting subacute osteomyelitis of the epiphysis and metaphysis is readily explainable in infants younger than 18 months, when one considers that vascular communication between the epiphysis and metaphysis is present until age 18 months, as described by Trueta.^[28] Epiphyseal lesions may also occur in older adolescents when the growth plate becomes attenuated and fails to provide a barrier to epiphyseal infection. Another interesting explanation for the localization of subacute osteomyelitis adjacent to the growth plate cartilage is the finding by Speers and Nade that S aureus has a certain affinity for physeal cartilage.^[29]

The transgression of the epiphyseal plate from osteomyelitis foci has been well documented (see images below). A review of the literature indicates that despite localized transgression of the epiphyseal plate by subacute osteomyelitis, growth plate arrest, stimulation, or development of transepiphyseal bony bars is exceedingly rare.

Contraindications to medical treatment alone for subacute osteomyelitis include the following:

• Failure of symptoms to resolve after an up to 6-week course of antibiotics or worsening of the condition during treatment
• Aggressive lesions (indistinguishable from malignant bone tumors)
• Impending sinus formation or drainage into a synovial joint
• Clinical signs of subperiosteal pus or synovitis

No literature exists to support medical treatment in adults, as subacute osteomyelitis mostly affects patients in the pediatric age group. Until medical treatment in adults is described, surgical treatment of subacute osteomyelitis is indicated.

No true contraindications to surgical intervention exist, as medical treatment alone without biopsy or curettage is still controversial in the literature.