18 Fungal and Tubercular Infections of the Thoracic Spine Abstract Fungal and tubercular infections of the thoracic spine are uncommon occurrences in developed countries. However, because of their slow and nonspecific presentation, diagnosis is often delayed and special vigilance is necessary for timely diagnosis. One should have a particularly high suspicion in patients with immunosuppression or those from endemic areas, and individuals presenting with atypical symptoms such as fever, weight loss, and focal tenderness. Once properly recognized, the mainstays of treatment are antifungal or antitubercular chemotherapy with reversal of immunosuppression as can safely be permitted by the patient’s clinical situation. Surgical debridement is often indicated in cases of fungal or tuberculous spondylitis, and in all cases where patients present with significant neurologic compression, unrelenting back pain, significant spinal instability, or deformity. Keywords: tuberculosis of spine, fungal spondylitis, tuberculous spondylitis, Pott’s disease, spinal coccidioidomycosis, spinal blastomycosis, spinal candidiasis, spinal aspergillosis Clinical Pearls • Fungal or tubercular infections of the spine should be suspected in patients who present with months of nonspecific back pain and have a history of immunosuppression or who hail from high-risk populations. • Evaluation with magnetic resonance imaging will often reveal extensive involvement of the anterior column of the spine, but relative sparing of the intervertebral disc. Spread between vertebrae along and underneath the anterior longitudinal ligament is common. • Treatment of tubercular infections can consist of medical therapy alone. However, most incidences of fungal infection and any case where there is significant neurologic deficit or deformity require surgical decompression and possible reconstruction. Fungus and tubercular infections of the thoracic spine are relatively uncommon. When they are encountered, however, they present unique challenges in both diagnosis and treatment that require special attention from clinicians due to its indolent nature. Diagnosis is often delayed due to the gradual and nonspecific nature of symptoms, factors which may be exacerbated by the complexity of immunosuppressed patients that are at particularly high risk for these infections. Treatment typically consists of prolonged antibiotic courses, but may also include neural decompression, debridement, deformity correction, and fusion of unstable elements when necessary. This chapter discusses the epidemiology, pathophysiology, presentation, diagnosis, and treatment of fungal and tubercular infections of the thoracic spine. Information is presented both on these infections in general, and on the specifics of the most commonly encountered organisms. Systemic fungal infection is an uncommon occurrence, with an estimated incidence of approximately 306 per 1,000,000 in the United States.1,2 This number has been increasing in recent decades, however, as the number of immunocompromised patients has increased.1,3,4,5 Risk factors for developing invasive mycoses include stem cell or solid organ transplantation, major surgery, severe polytrauma, severe burns, human immunodeficiency virus (HIV) infection, immunosuppressive therapy, disseminated malignancy, and advanced age. Fungal infections of the spine are rarer still, with data limited to individual case series. Fungal infections can further be subdivided into opportunistic infections, such as Candida species, Aspergillus species, Cryptococcus neoformans, and Pneumocystis jirovecii, and endemic infections such as Coccidioides immitis/posadasii and Blastomyces dermatitidis. This distinction affects presentation. Opportunistic infections require some break in the patient’s normal immune barriers, and are nearly always associated with recent exposure to the health care system, including systemic use of antibiotics, corticosteroids, tumor necrosis factor (TNF) alpha inhibitors, chemotherapeutic agents, chronic indwelling lines, and/or recent procedures.6 Endemic infections, on the other hand, can be acquired by simple exposure in the natural habitat and possess the inherent ability to invade deeper structures in otherwise healthy patients. Of note, Histoplasmosis capsulatum, though another endemic fungus that can cause invasive infection, will not be discussed as spinal involvement is exceedingly rare and typically only seen as part of a larger fungal meningitis.7 Systemic tuberculosis demonstrates a distinct disparity between the developed and underdeveloped populations. With an estimated prevalence of greater than 13 million worldwide, tuberculosis remains a global disease, with populations in Asia and Africa accounting for almost 90% of known cases.8 Spinal involvement is uncommon, but it occurs in approximately 1% of affected patients and the spine is the most common site of skeletal involvement.9,10,11 In the United States, tuberculosis remains rare, with an estimated incidence of 3 per 100,000. At-risk populations, including foreign-born residents (especially those from countries with high prevalence), immunocompromised patients, and those who are incarcerated or homeless, suffer disproportionately high rates of infection. Foreign-born residents from China (24.9 cases per 100,000), the Philippines (46.9 cases per 100,000), and Vietnam (47.8 cases per 100,000) have among the highest incidences of tuberculosis.12 The thoracic and thoracolumbar spines are disproportionately infected in fungal and tubercular infections as they spread through spore inhalation.13,14 Once a nidus of infection has been established in the lungs, dissemination to the spine occurs through either hematogenous or lymphatic spread.15,16 Venous drainage of the lungs via the bronchial veins and azygous vein or lymphatic drainage into the thoracic duct allows for an avenue of infectious spread into the paraspinal region. These, in turn, allow seeding into the cancellous bone of the spine via the external and internal venous plexuses, as well as intervertebral spread via either contiguous infection or through Batson’s plexus. Arterial seeding, through gross fungemia and access through the radicular arteries and subchondral perforators of the spine, has also been hypothesized.15 Once there, infection causes symptoms through either structural compromise of the trabecular bone leading to instability, abscess formation and subsequent neural compression, or vascular thrombosis with resulting infarction. Because infections preferentially affect the anterior column of the spine, immediate or delayed progressive kyphotic deformity is not uncommon. This is of particular concern in pediatric patients, who are still developing their axial skeleton and whose normal anterior column growth can be hampered by the infection. Thus, many pediatric cases warrant complex reconstruction.17 Direct intradural or intraparenchymal invasion is rare, but is associated with high morbidity.18,19,20 In immunosuppressed individuals, the lack of both T-cell immunity and TNF alpha activation appears to be particularly crucial factors in pathogenesis. CD4+T cells have been shown to be critical in initial recognition of invasive fungal species of the lungs. After they encounter pathogen epitopes, these CD4+cells are activated, and in turn activate macrophage phagocytic activity through toll-like receptor-mediated signals.21 Similarly, TNF alpha activation is responsible for a wide range of immunoregulatory functions, including antitumor and antiviral responses. This holds true for Mycobacterium tuberculosis infection, where it serves a special role in stimulating recruitment of immune cells to the infected region and initiating granuloma formation. TNF alpha inhibition has been shown to interfere with granuloma formation and to cause lysis of fully formed granulomas in mice.22 Use of TNF alpha inhibitors is associated with extrapulmonary tuberculosis, with extrapulmonary disease evident in 57% of those with TNF alpha inhibition-related tuberculosis activation.23 As with many types of spinal infections, fungal and tubercular involvement of the spine can be difficult to diagnose due to the slow onset and nonspecific nature of symptoms. Back pain is common, but is frequently mistaken for more benign pathologies. A high index of suspicion should be maintained in patients from at-risk populations, and those who present with atypical or concerning symptoms should merit further work-up ( A proper history and physical is crucial for proper patient evaluations. History-taking should elucidate the time course and progression of symptoms and any associated neurologic complaints. Signs of and risk factors for infection should be identified, including a proper travel history and social history. Cancer patients should have their current treatment details explored. Patients actively undergoing chemotherapy or bone marrow transplantation present a substantially elevated risk than those with stable disease. Patients who have been infected with HIV should have the status of their infection (including CD4+ cell counts and viral loads) identified, and updated if necessary. Medication lists can also be illuminating, in particular, if a patient has been on long-term corticosteroids or TNF alpha inhibitors. Table 18.1 Risk factors and warning signs in patients with fungal and tubercular spondylitis
18.1 Introduction
18.2 Epidemiology and Pathophysiology
18.3 Presentation and Evaluation
Table 18.1).
At-risk populations | Warning signs on presentation |
• Incarcerated • Homeless • Immunocompromised ◦ Infected with human immunodeficiency virus ◦ Ongoing chemotherapy with myelosuppression ◦ Congenital immunodeficiency ◦ Status post organ transplantation ◦ Iatrogenic immunosuppression with corticosteroids or TNF alpha inhibitors • Foreign born from endemic areas • Concerning presentation + recent travel to endemic regions • Previous systemic fungal or tubercular infection • Diabetes mellitus • Intravenous drug use | • Fever • Malaise • Recent weight loss • Night sweats • Progressive neurologic deficit • Symptoms of spinal instability in young patients • Gross kyphotic deformity • Back pain resistant to standard therapy |
Abbreviation: TNF, tumor necrosis factor. | |
Physical examination should seek to not only identify the site of a potential lesion, but also to document the severity and extent of any neurologic deficits. Examination of the lungs can often be revealing, especially if a focal area of aeration is detected. Focal tenderness to palpation along the spine can indicate involved levels, and may indicate spread to the posterior elements or paraspinal tissues.
As in many spine cases, and especially in patients suspected of having an infectious spondylitis, the next stage in evaluation should be to pursue imaging. Both magnetic resonance imaging (MRI) and computed tomography (CT) are important to characterize the extent of bony and neural involvement, as well as the integrity of osseous structures. Standing plain radiographs can also be useful to assess the degree of any associated deformity and sagittal imbalance.
On MRI, fungal and tubercular abscesses bare similar characteristics, and can be difficult to differentiate from more commonly encountered pyogenic infections. Both tuberculous and fungal spondylitis are marked by preferential involvement of the anterior column, large paraspinal abscesses, and importantly, relative sparing of the intervertebral discs (
Fig. 18.1).24,25,26 The inflammatory reaction to infectious spondylitis results in bony edema, resulting in decreased signal on T1-weighted imaging and increased signal on T2-weighted imaging in the marrow of the vertebral bodies (
Fig. 18.2).27 Contrast enhancement is typical, but oftentimes can be nonspecific. The infection can often be seen spreading underneath, but contained by, the anterior longitudinal ligament. The relative sparing of the disc and ligament, particularly classic for tuberculous spondylitis, is thought to be due to the relative lack of proteases of the organism, preventing direct invasion through ligamentous structures.28,29 Multilevel involvement is common, and can help differentiate infection from osseous tumor involvement, which can appear similarly (
Fig. 18.3).30 Epidural extension can be seen, and can often be characterized by a thin, smooth, abscess wall.31 Direct invasion of the dura with intradural abscess is an uncommon finding (
Fig. 18.4).
Fig. 18.1 Imaging from a 30-year-old patient who was born in China and presented with several months marked back pain. Fine-needle aspiration of the paravertebral fluid was positive for tuberculosis. (Left) T2-weighted sagittal MRI demonstrating involvement at the T8, T9, and T10 levels, with T9–T10 discitis, relative sparing of the T8-9 disc space, and contiguous subligamentous spread anteriorly. (Middle) Contrast-enhanced T1-weighted image demonstrating a characteristic large paravertebral abscess. (Right) Sagittal CT image demonstrating preferential lytic destruction of the anterior portion of the vertebral body.
Fig. 18.2 Images from a 30-year-old man with a history of hepatitis C, intravenous drug use, and insulin-dependent diabetes mellitus. He originally presented with weeks of sharp lower thoracic back pain with radiation into his testicles. (Left) MRI demonstrated hyperintensity on T2-weighted imaging in the T11 and T12 vertebral bodies with associated subligamentous spread. (Middle) T1-weighted contrast-enhanced imaging demonstrated relative preservation of the associated disc space suggestive of fungal or tubercular disease. (Right) Axial image demonstrated anterior paravertebral extension of disease. Needle aspiration of the lesion leads to the eventual diagnosis of Candida albicans spondylitis.
On CT imaging, extensive lytic destruction with bone sequestration is characteristic, with loss of the adjoining cortical definition.27,32 Calcifications in adjoining paraspinal abscesses can be seen in tuberculosis cases, which is pathognomonic for the disease.31
In addition to the above, it is important to consider other work-up in suspected cases. A plain chest radiograph can often be the most rapid way to establish a site of primary infection. As hematogenous spread is common, blood samples to look for fungemia or systemic tuberculosis can be useful to establish a diagnosis. Imaging of the rest of the body with CT imaging can also identify other extrapulmonary lesions and help guide systemic treatment. Systemic inflammatory markers, though nonspecific, can also help mark response to therapy going forward. Often times, however, the above work-up is either nonspecific or too slow. Thus, when necessary, image-guided needle biopsy aspiration can confirm the diagnosis and help set up a proper treatment strategy.
18.4 Organism-Specific Considerations
18.4.1 Tuberculosis
M. tuberculosis remains widely prevalent and a major cause of spinal infections in many parts of the world. Of all cases of tuberculosis, approximately 15 to 20% affect extrapulmonary locations.33 With regard to the central nervous system, it is well known for manifesting as an indolent meningitis or spondylitis (i.e., Pott’s disease), although tuberculomas may also present as focal intraparenchymal and intradural extraparenchymal lesions of the brain and spinal cord. The spine is involved in 50% of cases of skeletal spread, accounting for up to 1% of tuberculosis infections.33,34 Pott’s disease most commonly affects the thoracic spine.9,35
