8 Spinal Tuberculosis: Pathogenesis, Clinical Features, and Investigations
Introduction
Chronic infections of the vertebral column are usually granulomatous and are caused by mycobacteria, fungi, and Brucella species. Among these, tuberculous infection of the spine is the most common. Due to the high vascularity of the vertebral marrow, the tuberculous bacilli have a predilection to afflict the vertebral column, which is the second most common site of tubercular infection after the lungs. Tuberculous infection of the spine usually happens secondary to a primary infection elsewhere, such as the lungs, lymph nodes, kidneys, or the gastrointestinal tract.
Typical symptoms of spinal tuberculosis (TB) include chronic pain at the affected site associated with constitutional symptoms of fever, malaise, and weight loss. In advanced stages of the disease, kyphotic deformity and neurologic deficit can develop. Diagnosis is usually straightforward in endemic regions based on the typical symptoms and signs. But confirmation of the diagnosis through appropriate investigations is essential in view of the growing incidence of drug-resistant TB. There is also a possibility of other pathologies such as pyogenic infections, fungal spondylitis, lymphoproliferative disorders, and spinal metastasis, which may have a similar presentation. A combination of diagnostic tests, including radiographs, magnetic resonance imaging (MRI), the GeneXpert test, tuberculous culture, and histopathological examination, is helpful in confirming the diagnosis. Antitubercular chemotherapy is the mainstay of treatment that has significantly improved the outcome for patients. Although most patients are treated only with chemotherapy, surgery is indicated in specific situations, such as extensive destruction, spinal instability, and gross neurologic deficit. Currently, co-infections with human immunodeficiency virus (HIV) and the drug-resistant TB are major stumbling blocks in the global war against TB.
Epidemiology
Despite significant efforts by global health care organizations and governmental disease control programs, the global burden of TB still remains enormous. According to the World Health Organization (WHO) Global TB report in 2015, there were an estimated 10.4 million new (incident) TB cases worldwide. 1 People living with HIV accounted for 1.2 million (11%) of all new TB cases. Six countries accounted for 60% of the new cases: India, Indonesia, China, Nigeria, Pakistan, and South Africa. In 2015, there were an estimated 490,000 new cases of drug-resistant TB, of which India, China, and the Russian Federation accounted for 45% of cases. There were an estimated 1.4 million TB deaths in 2015, and although the number of TB deaths fell by 22% between 2000 and 2015, TB remains one of the top 10 causes of death worldwide in 2015.
India, China, and South Africa share the major burden of spinal TB, too. In the developing parts of the world, the incidence is higher because of the crowded conditions, poor sanitation, reduced access to health care, and the lack of knowledge about TB among the people and the health care workers. In India, there are 6 million radiologically proven cases of TB, of which nearly 0.5 to 1% are vertebral TB. 2 In developed nations, spinal TB seems predominantly distributed among migrants. An epidemiological study of bone and joint TB conducted by Talbot et al 3 in the United Kingdom found that 74% of 756 patients diagnosed with TB were immigrants from the Indian subcontinent.
Pathogenesis
Tuberculosis is caused by a bacillus of the Mycobacterium tuberculosis complex, which includes M. tuberculosis (the most common), M. avis, M. bovis, and M. intracellulare. Most infections are caused by the M. tuberculosis, which is a slow-growing aerobic bacillus with a lipid and peptidoglycan-rich cell wall, which prevents it from being destroyed by the host immune system.
Vertebral infection usually occurs following hematogenous dissemination of the bacillus from a primary infective focus such as the lungs. Rarely, the bacilli may also travel from the lung to the spine through the paravertebral venous plexus or by lymphatic drainage from the adjoining nodes. Within the spinal column, most infections occur around the lower thoracic and thoracolumbar junction (50–70%), followed by the thoracic spine (20–30%). 4
Once they reach the vertebral marrow, the bacilli get lodged in the subchondral zone on either side of the disk, because the paradiskal arteries split on either side of the disk to reach the upper and lower end plates of each disk. This is the “paradiskal” type of infection, and it is the most common pattern of tubercular spinal infection. The intervertebral disk is not involved primarily, but progressive destruction of the vertebral end plates results in direct spread of infection into the disk. Progressive destruction results in collapse of the vertebral body, leading to kyphosis and pathological fractures. Vertebral body collapse can sometimes affect even two or three contiguous vertebral bodies, resulting in severe kyphosis. The combination of kyphosis, pathological collapse with retropulsed bony fragments, and exuberant abscess formation can compress the spinal cord, resulting in a neurologic deficit. Due to the chronic inflammatory response, extensive abscess formation is typical of TB. The abscess contents slowly spread into the epidural, prevertebral, and paravertebral regions and produce characteristic signs and symptoms.
The second most common pattern is called the centrum type, wherein the infection occurs predominantly within one vertebral body, resulting in complete collapse of the body with sparing of the disks on either side. Extensive involvement with complete destruction of many adjacent vertebral bodies is more commonly seen in children, due to the cartilaginous nature of their bones. In severe cases, this presentation may mimic vertebra plana (complete collapse of one vertebral body), which can occur in other conditions such as histiocytosis and spinal tumors. The presence of extensive abscess formation near the collapsed vertebral body and multifocal involvement helps in differentiating this type from other causes of vertebra plana ( Fig. 8.1 ).
A third pattern is infection of the posterior elements, wherein the pedicles, facet joints, spinous process, and lamina are affected alone, with sparing of the vertebral body ( Fig. 8.2 ). It is uncommon (< 1%). Diagnosis of posterior-element TB is difficult with conventional radiographs alone, and often requires an MRI instead. 5 A fourth pattern, non-osseous, is also very rare, characterized by extensive abscess formation without much bony vertebral damage. It is typically described around the sacroiliac joints and the lower lumbar region.
Microscopic Features
Microscopically, the characteristic pathological lesion of TB is called the tubercle, based on which a confirmatory diagnosis is made by histopathological examination. The tubercle is composed of inflammatory cells, cellular debris, necrotic material, and fibrous tissue. As the bacilli infiltrate the vertebral marrow, the initial immune response is characterized by acute inflammation with polymorphonuclear cells. As the neutrophils are unable to control the tubercular bacilli, a chronic inflammation results, characterized by the infiltration of macrophages and monocytes. Although the tubercle bacilli are phagocytosed by the macrophages, the thick cell wall prevents the death of the bacilli. The macrophages slowly transform into epithelioid cells, which are seen in histopathological images as elongated cells with fine granular, pale eosinophilic cytoplasm and a central, ovoid nucleus. In late stages, the epithelioid cells often merge, forming multinucleated giant cells. These giant cells, referred to as the Langhans giant cells, are one of the characteristic microscopic features of tuberculous lesion. This lesion of TB formed by macrophages, epithelioid cells, Langhans giant cells, and lymphocytes is called the tubercle (from which the disease gets its name). With progressive destruction, caseation necrosis occurs in the center of the tubercle due to proteolytic destruction by the enzymes released by the macrophages. Adjacent tubercles coalesce to form large abscesses lined by a thin reactive capsule.
Clinical Features
Unlike pyogenic infections of the spine, a tuberculous lesion has a much more insidious onset, and the clinical symptoms often develop over a period of 1 to 2 months. It is a systemic disease, and often infection of multiple organs can coexist. An active concomitant primary tubercular infection in the lungs, lymph nodes, intestines, and kidneys can be present, and should be evaluated through history and clinical examination. Similarly, the lesion can be present in other skeletal regions and in multiple regions of the spine.
Constitutional symptoms of malaise, loss of appetite and weight, evening rise of temperature, and night sweats are typical systemic features of TB. However, in patients with spinal TB, systemic symptoms may not be common. One study reported weight loss in 58% patients, and other constitutional symptoms such as malaise and loss of appetite were observed in 70% of cases. 6
At the vertebral site of tuberculous infection, the classical clinical presentation involves a tetrad: pain at the affected site, neurologic deficit, abscess formation, and kyphotic deformity.
Pain in Spinal Tuberculosis
Axial pain associated with spinal stiffness is the most common presenting symptom. In different studies, 90 to 100% of patients with spinal TB had back pain. 7 Axial pain in spinal TB is caused by the tubercular inflammatory response, spinal instability (due to destruction of the stabilizing vertebral structures), and periosteal distension (caused by the tubercular abscess). In the early stages, the pain is dull and aching, insidious in onset, and often well controlled by analgesics. However, as spinal instability develops, the intensity of the pain increases. Patients with spinal instability due to thoracic and lumbar TB may need to support their trunk by placing their hands on the couch while sitting (“ tripod sign”). Patients with cervical instability due to TB may need to hold their neck with their hands. Due to inflammation and venous engorgement in supine posture, patients with spinal TB have severe pain at night and, in the worst situations, this can manifest as “night cries.” The lack of a protective muscle spasm during sleep can result in sudden pathological movement across the destroyed bones, causing severe pain. Radicular pain is an uncommon feature and indicates compression on the nerve roots due to abscess or free bone fragments.
Kyphosis
As the disease progresses, gradual destruction of the vertebral body occurs, which results in a localized kyphotic deformity. The severity of kyphosis varies, depending on the extent of the vertebral body damage. Single (isolated) vertebral collapse results in a knuckle deformity, whereas destruction of several vertebrae results in “gibbus” (collapse of two to three vertebrae) or angular kyphosis (multiple vertebral collapse). The vertebral bodies at the apex of kyphosis can retropulse into the canal, causing neurologic deficit. With progressive destruction and further destabilization, chronic vertebral subluxation and translations can occur, further compromising the spinal canal. Lesions of the cervical and lumbar region tolerate vertebral destruction without much local kyphosis due to their inherent lordosis, whereas thoracic lesions present earlier with significant deformity.
The development and progression of kyphosis differ in children and adults. 8 In adults, the kyphosis progresses only during the active phases of the disease, and the severity of the kyphosis depends mainly on the extent of vertebral body damage. But in children, the kyphosis progresses more rapidly during the active phase because of their soft bones. Further, the kyphosis present at the end of vertebral healing can worsen during the remaining period of growth even after curing the disease. This has been observed in 40% of children in a longitudinal study. 9 Hence, children with healed TB need periodic follow-up until their growth is completed. Rajasekaran 9 has described four spine at-risk signs as indicators for progressive kyphosis; children with two of the signs were found to be at serious risk of a gross increase in deformity.
Related posts:
Stay updated, free articles. Join our Telegram channel
Full access? Get Clinical Tree
