What is the cause, pathogenesis, clinical presentation, diagnostic work‑up, and management of spinal tuberculosis (Pott disease)?

Spinal Tuberculosis (Pott Disease): Comprehensive Overview

Cause and Pathogenesis

Spinal tuberculosis is caused by hematogenous spread of Mycobacterium tuberculosis from a primary focus (typically pulmonary or abdominal) to the vertebral column, representing approximately 50% of all skeletal tuberculosis cases. 1, 2

Mechanism of Infection

• In adults, infection initially invades the vertebral endplate via hematogenous route, centering on the vertebral body (osteomyelitis) and subsequently involving the intervertebral disc (discitis) due to shared segmental arterial supply 1, 2
• The paradiscal type (involving adjacent vertebrae and intervening disc) is the most common pattern of spinal tuberculosis 3
• Progressive destruction of the anterior vertebral body leads to vertebral collapse, kyphotic deformity (gibbus), and potential neurological compromise 2, 4
• Epidural and paraspinal soft tissue involvement with cold abscess formation occurs in 69% of cases 5

High-Risk Populations

• Patients from tuberculosis-endemic regions (Turkey, Egypt, Albania, Greece, South Asia, Africa) 1, 5
• Immunocompromised hosts: HIV infection, diabetes mellitus, chronic renal failure, malignancy, immunosuppressive therapy 1
• History of prior tuberculosis exposure or concomitant visceral tuberculosis 4

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Clinical Presentation

The clinical presentation is characteristically insidious and indolent, with median duration from symptom onset to diagnosis of 78 days, contributing to significant diagnostic delay and morbidity. 5

Cardinal Symptoms

• Back pain (most common presenting symptom): localized, progressive, worse at night 1, 4
• Constitutional symptoms: fever (often low-grade), weight loss, anorexia, fatigue, malaise 5, 6, 4
• Neurological deficits occur in 40% of patients at presentation, ranging from radiculopathy to complete paraplegia (Pott's paraplegia) 5, 2

Physical Examination Findings

• Tenderness on palpation of spinous processes is the most rewarding clinical finding and invaluable for early recognition 4
• Visible or palpable spinal deformity (kyphosis/gibbus) in advanced cases 5
• Neurological examination may reveal motor weakness, sensory deficits, or sphincter dysfunction 4

Common Complications at Presentation

• Cold abscess formation: 69% (paraspinal, psoas, epidural) 5
• Neurological deficits: 40% (paraparesis to paraplegia) 5
• Spinal instability: 21% 5
• Spinal deformity: 16% (kyphosis, gibbus, scoliosis) 5

Anatomical Distribution

• Lumbar spine: 56% (most common site) 5
• Thoracic spine: 49% 5
• Thoracolumbar junction: 13% 5
• Multiple level involvement occurs in 51% of cases, with 8% showing noncontiguous (skip) lesions 1, 5

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Diagnostic Work-Up

A high index of clinical suspicion is required to initiate the diagnostic workup, as imaging findings may overlap with degenerative disease, neoplasm, or pyogenic infection. 1

Laboratory Evaluation

Essential baseline tests include:

• Erythrocyte sedimentation rate (ESR): highly sensitive, typically elevated in spine infections 1, 7
• C-reactive protein (CRP): more specific than ESR, rises rapidly with infection; CRP >100 mg/L indicates very high suspicion for active spinal infection 7
• White blood cell count with differential: may be normal in up to 40% of cases, making it less reliable than ESR/CRP 7
• Blood cultures: obtain before starting antibiotics to identify causative organisms 1, 7
• Mycobacterial testing (tuberculin skin test, interferon-gamma release assays) in patients from endemic areas or with risk factors 1

Imaging Studies

MRI with contrast is the gold standard imaging modality for suspected spinal tuberculosis, providing superior soft tissue detail and defining extent of disease 1

MRI findings characteristic of spinal tuberculosis:

• Vertebral body destruction with relative disc preservation (early stages) 2
• Subligamentous spread involving multiple contiguous vertebrae 2
• Large paraspinal or epidural abscesses (often disproportionate to bone destruction) 1
• Spinal cord compression or myelitis 1

CT imaging is useful for:

• Defining bony destruction and guiding percutaneous biopsy 1
• Assessing spinal stability 1
• Patients unable to undergo MRI 1

Plain radiographs show late findings:

• Vertebral body destruction, disc space narrowing, kyphotic angulation 2
• Limited sensitivity for early disease 1

Consider imaging the entire spine in:

• IV drug users 1
• Patients with tuberculosis (higher risk of multilevel involvement) 1
• Initial imaging showing multifocal disease 1

Microbiological Confirmation

Image-guided aspiration biopsy should be performed to confirm diagnosis and determine drug susceptibility before initiating treatment 8

Biopsy specimens should be sent for:

• Gram stain and aerobic culture 7
• Mycobacterial stain (acid-fast bacilli) and culture 7
• Nucleic acid amplification testing (PCR for M. tuberculosis) 8, 6
• Fungal stain and culture 7
• Histopathologic examination (looking for caseating granulomas) 1, 5

Critical considerations:

• Hold antibiotics for 1-2 weeks prior to biopsy to increase diagnostic yield, except in cases of neurological compromise or hemodynamic instability 8
• The causative agent is identified in only 41% of cases due to paucibacillary nature of spinal tuberculosis 5, 3
• Histopathologic examination consistent with tuberculosis in 74% of biopsied cases 5

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Management

Medical Treatment

The standard treatment consists of a 6-month regimen of rifampicin and isoniazid, supplemented with pyrazinamide and ethambutol for the first 2 months (2HRZE/4HR). 8

First-Line Regimen for Drug-Susceptible Tuberculosis:

Intensive Phase (2 months):

• Isoniazid (H)
• Rifampicin (R)
• Pyrazinamide (Z)
• Ethambutol (E)

Continuation Phase (4 months):

• Isoniazid (H)
• Rifampicin (R)

Critical treatment principles:

• Daily dosing is strongly recommended over intermittent regimens 8, 9
• Fixed-dose combinations may provide more convenient administration and improve adherence 8, 9
• If pyrazinamide cannot be tolerated, extend treatment to 9 months 8

For children with Pott's spine:

• Treatment should be extended to 12 months for bone/joint tuberculosis due to insufficient data on shorter regimens 9
• Do not delay treatment initiation in young children waiting for microbiological confirmation, as disease can rapidly disseminate 9

Drug-Resistant Tuberculosis

For multidrug-resistant TB (MDR-TB), treatment must be guided by drug susceptibility testing and managed by or in close consultation with TB experts. 8, 9, 3

Empirical regimen for suspected drug resistance:

• Fluoroquinolone (moxifloxacin or levofloxacin) 8
• Injectable agent (if not previously used): amikacin, kanamycin, or capreomycin 8
• Additional oral agents: cycloserine, ethionamide, or para-aminosalicylic acid (PAS) 8

Critical principle: Never add a single new drug to a failing regimen to prevent further acquired resistance 8, 9

Surgical Management

Surgery is indicated for:

• Neurological compromise or spinal cord compression 8, 5
• Spinal instability 8, 5
• Significant kyphotic deformity 8, 5
• Large abscess formation requiring drainage 8
• Failure to respond to medical therapy 8

Surgical approaches include:

• Debridement of infected tissue 8, 2
• Abscess drainage 8
• Spinal fusion and stabilization 2
• Correction of spinal deformity 2

10% of patients require more than one surgical intervention 5

67% of patients undergo diagnostic and/or therapeutic surgical intervention, while 33% are managed with medical treatment alone 5

Monitoring and Follow-Up

Treatment response monitoring:

• CRP improves more rapidly than ESR and correlates more closely with clinical status 7
• After 4 weeks of treatment, CRP >2.75 mg/dL (27.5 mg/L) may indicate treatment failure and significantly higher risk of recurrence 7
• Follow-up imaging to evaluate response and detect complications 8

For children:

• Long-term follow-up is essential, as spinal growth can exaggerate deformities years after treatment completion 8, 9
• Clinical assessment at baseline and months 1,2,3,4,5,6,9,12,15,18, and ongoing 9
• Measure height and weight regularly 9

Monitor for drug-related adverse effects:

• Hepatotoxicity (isoniazid, rifampicin, pyrazinamide) 8
• Visual disturbances with ethambutol (optic neuritis) 8

Adjunctive Therapies

• Directly Observed Therapy (DOT) is recommended to ensure adherence 8
• Nutritional support, especially for malnourished patients 8
• Intensive physiotherapy and rehabilitation are essential for improving function and preventing complications 8, 9
• Orthotic devices may be needed to support the spine during healing 8

Special Populations

HIV co-infection:

• Antiretroviral therapy should be initiated within 2 weeks of starting TB treatment 8, 9
• Monitor for immune reconstitution inflammatory syndrome (IRIS), which may respond to corticosteroids 8, 9

Diabetic patients:

• More frequent glucose monitoring required, as TB disease and some TB drugs can disrupt glycemic control 8

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Prognosis and Outcomes

Neurological recovery can be expected in most cases if treatment is initiated before irreversible cord damage occurs. 8

Mortality and morbidity:

• Mortality rate: 2% 5
• 25% develop sequelae despite treatment 5

Distribution of post-treatment sequelae:

• Kyphosis: 11% 5
• Gibbus deformity: 6% 5
• Scoliosis: 5% 5
• Paraparesis: 5% 5
• Paraplegia: 5% 5
• Loss of sensation: 4% 5

Predictors of unfavorable outcome:

• Older age 5
• Presence of neurological deficit at presentation 5
• Spinal deformity at presentation 5

Affected vertebrae may continue to show radiographic changes during treatment without indicating treatment failure 8

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Common Pitfalls and Caveats

Diagnostic pitfalls:

• Diagnostic delay is common due to insidious presentation with nonspecific symptoms (back pain, fever), with median time to diagnosis of 78 days 1, 5
• Relying solely on WBC count is misleading, as it may be normal in up to 40% of patients; ESR and CRP are more reliable 7
• Imaging findings may overlap with degenerative disease, neoplasm, or pyogenic infection, requiring biopsy for confirmation 1
• Missing multifocal or noncontiguous involvement (occurs in 8% of cases) requires comprehensive spinal imaging in high-risk patients 1, 5

Treatment pitfalls:

• Treatment failure is often due to poor adherence, drug resistance, or inadequate duration of therapy 8
• Do not use shorter than 12-month regimens for spinal TB in children due to insufficient evidence 9
• Never add a single drug to a failing regimen, as this promotes further resistance 8, 9
• Do not discontinue monitoring after treatment completion, as spinal deformities can worsen with growth over many years in children 8, 9

Geographic considerations:

• Tuberculosis is the most common cause of spinal infections worldwide, but in developed countries, it is more commonly seen in immigrants from endemic areas 8
• Consider tuberculosis in the differential diagnosis of vertebral osteomyelitis, especially in endemic regions 5