Back pain is a very common presenting complaint at primary care level, and it is vital to separate pathological back pain from regular mechanical back pain, whilst managing busy clinics.²⁹ The Adult Primary Care Guidelines of 2016–2017 recommend standard subjective and objective techniques for use in the initial assessment of a patient,³⁰ including important information about the patient’s beliefs, fears and concerns. We propose two initial questions that may add information: ‘Please tell me more about your back pain and why you are here today?’ and ‘Do you have specific reasons to be more concerned about this back pain than you would about other kinds of back pain?’ These could highlight elements of the objective assessment that need closer scrutiny.

When the patient is given time to answer these suggested questions, the clinician is then able to listen for symptoms that may indicate STB. Symptoms of STB are notoriously unspecific and, although certain symptoms can be present, their absence does not exclude the diagnosis. The most common presentation of STB is spinal or referred radicular pain in 85% – 100% of cases,^{5,17,18,29,31} with the highest proportion of cases presenting in the lumbar, thoracic or thoracolumbar regions, followed generally by cervical, lumbosacral, cervicothoracic, sacral or craniocervical.^3,31,32,33 In 24% – 56% of cases, constitutional symptoms are present,^{5,17,19,21,29} with weight loss reported in 36% – 48% of cases.^5,32 Neurological signs (indicative of more progressive disease) are reported in 21% – 85% of cases.^{5,18,21,31,32,34}

One study from China including 89 people with mild STB in a cohort of 740 with STB provides further information on symptoms that may assist in the identification of STB. The criteria for the classification early in this study included, in some ways, quite advanced disease, with amongst others mild neurology, a kyphosis or gibbus of ≤ 30° and up to three levels of vertebral involvement. The presenting symptoms of these early cases were spinal pain at the site of infection (97%), night sweats (37%), low grade fever (28%), weight loss (44%), restricted movement (90%), percussion pain (99%), local deformity (11%) and sinus (2%). This study accepted cases that were diagnosed on response to treatment without identification of Mtb.¹⁵ The well-informed clinician will recognise that many of the above symptoms are also associated with other pathologies.

Red flag questions used in isolation, in the absence of clinical reasoning around the full context of a patient, have been questioned, even in regard to screening for spinal malignancy.³⁵ The risk factors that need to be in the forefront of each health care worker’s mind in a TB endemic country are as follows: children complaining of back pain, immunocompromising states (pregnancy, being elderly, drug and alcohol abuse, steroid treatment, post–organ transplant and poverty), immunocompromising illnesses (HIV, diabetes mellitus, renal failure, rheumatoid arthritis, cirrhosis, Systemic Lupus Erythematosus (SLE) and cancer), back pain > 3 months, age < 20 or > 50, bladder or bowel dysfunction, saddle paraesthesia and a history of cancer.^{5,19,20,36,37,38,39,40} Details about the start date of ART and of the level of immune system compromise at that date enables evaluation of the risk of an unmasking IRIS, which can present within months after starting or changing ART.^11,32

In the diagnostic process, the clinician must consider the following conditions: pyogenic or fungal vertebral osteomyelitis, brucellar spondylitis, multiple myeloma, lymphoma, metastatic disease, osteoporotic vertebral fractures, atypical degenerative disc disease, sarcoidosis, other primary tumours (acute myeloid leukaemia, angiosarcoma, angioblastoma, giant cell tumour, osteochondroma) or aneurysmal bone cyst.^24,27,41,42

Observing the site of pain and ability to move at that area (with the patient undressed) is accepted as part of a minimal assessment and is also particularly pertinent to the diagnosis of STB.¹³ We suggest that localised point pain indicative of a STB lesion is often identified by the patient demonstrating the site of pain with a single finger as opposed to a whole hand. Zhang reported percussion pain as one of their positive findings in people with early STB.¹⁵ Basic observation includes an accurate assessment of the patient’s weight to identify weight loss. Weight gain can be used later as an indicator of response to treatment.

Following the completion of the standard subjective and objective examination of the patient, several additional tests are recommended in the literature for use in patients where there is a concern of STB; these include sputum and HIV testing, Erythrocyte Sedimentation Rate (ESR), C-reactive protein (CRP), platelets, white cell count (WCC) and alkaline phosphatase.²⁹ These are useful in the diagnosis of STB, although they are not diagnostic of STB in themselves. The high clinical utility of blood tests means these can be applied at primary clinic level with results reviewed on a return visit, thus reducing diagnostic delays and improving affordability and patient accessibility.

Sputum: As 14% – 37% of people with STB are co-infected with PTB,^9,19,29 sputum or an induced sputum (using a nebuliser in the open air with 3% hypertonic saline if negative pressure rooms are not available) should be sent for culture and analysed with GeneXpert.⁴³ A positive sputum indicates the need for TB treatment, but further exploration is necessary to determine the length of treatment required. It must be noted that a negative sputum result does not rule out STB.^2,3,17,44,45 Therefore, a sputum sample should be obtained from every patient in whom STB is suspected.

HIV, CD4, antiretroviral therapy history and viral load: Because of the increased risk that concomitant HIV poses, an HIV test is indicated for patients at risk or in those who do not know their status. A positive status indicates the need to assess their CD4 levels. If the patient is taking ART, it is important to assess viral load for viral suppression. If the patient has recently started ART or changed regime, he or she has an increased risk of IRIS.

Erythrocyte sedimentation rate, C-reactive protein and platelet count: A raised ESR can assist in diagnosis and can be used to monitor response to treatment in culture-proven cases, but it is not specific to STB.^{5,14,19,24,31,32,34} A point-of-care ESR is possible at certain PHC clinics with test results available within one hour, removing the need for a repeat visit to the health facility. However, the interpretation of an ESR needs to be carefully considered for several reasons. The accuracy of an ESR might be affected by room temperature⁴⁶ and HIV affects ESR, possibly obscuring the results.^26,33,47 However, Daniel and Dunn reported no difference in the ESR of 57 HIV-infected STB patients compared with 21 STB patients uninfected with HIV. Therefore ESR is still recommended as a useful diagnostic clue and indicator of response to treatment, even in HIV positive patients.⁴⁸

Finally, it must be noted that an ESR may be increased for reasons other than STB, and a low ESR does not exclude STB (normal ESR reported in 11% – 12% of cases).^5,19 As an alternative inflammatory marker, CRP may also be useful to inform diagnosis. A raised CRP has been observed in between 90% and 100% of STB cases but, as with the ESR, it is not specific to STB and may indicate some other inflammatory or infective process.^9,19,29,48 In addition, a raised platelet count has been observed in people with STB, in both those infected and uninfected with HIV.⁴⁸ Therefore ESR, CRP and platelet count are useful tests to assist in the clinical reasoning around a patient presenting with spinal pain, suggesting that an infective process is present.

White cell count, haemoglobin and alkaline phosphatase: A normal WCC is typical in STB, indicating that the spinal infection is less likely to be pyogenic in nature, and an anaemic picture is common in the majority of STB presentations.^4,27,29,48 An elevated alkaline phosphatase may also suggest the presence of STB. However, based on the small sample this result was reported in (21 cases), we cannot make a strong recommendation on its use.²⁹ Finally, it must be noted that the Mantoux tuberculin skin test (TST) is not useful in TB endemic country or where the Bacillus Calmette–Guérin (BCG) vaccine is administered. HIV and other immunosuppressive conditions can lead to false negative readings of the TST.^26,49 Therefore, the usefulness of the TST in people with suspected STB in South Africa is not supported by the literature.

Terminology for people with suspicion of spinal tuberculosis: As the patient is investigated further for STB, Jain suggests the label of a ‘spine under observation’ may be a useful term to use.²³ We suggest that at the primary level of care this label would facilitate completion of investigations, decrease risk of inaccurate labelling of the patient and decrease the risk of assumption that the diagnosis has been confirmed until such time as the diagnosis is finalised.

Role of doctor, physiotherapist and speech therapist: Following the above investigations conducted by a clinical nurse at the primary level of care, further information could be gained with a referral for assessment to the outreach physiotherapist and doctor who visit the clinic, as well as the speech therapist if swallowing difficulties, stridor or hoarseness of voice are present in patients complaining of neck symptoms.^20,50,51 Full neurological examination including sensation, reflexes and muscle power by the nurse, doctor, physiotherapist and/or speech therapist is essential, because early cases of STB can present with neurological signs of which the patient themselves are unaware.^12,52 If the services of these professionals are not available at clinic level, referral should be made to the district hospital.

All patients with the suspicion of STB should be referred for radiographs (X-rays), which remain the mainstay of diagnosis because of their affordability and accessibility, particularly in developing countries,²⁴ and despite the superior sensitivity and specificity of MRI.^4,5,22 Polley and Dunn recommend that the entire spine be radiographed in all STB suspects.⁵³ In addition, chest radiographs should be performed simultaneously, although it is possible that people with proven pulmonary tuberculosis may have unremarkable chest radiographs.⁵⁴

Radiographs are useful for showing both vertebral destruction as well as soft tissue shadows. Jain noted that radiographs can reveal increased prevertebral soft tissue shadows in 7 out of 11 cases of cervical and cervicothoracic lesions.⁵⁵ Rivas-Garcia et al. recommend that oblique views be included in order to detect early changes that involve anterolateral corners of the vertebra.⁴¹

The limitations of radiographs have been demonstrated in numerous studies with MRI shown to be more accurate for identifying the number of levels involved and extent of soft tissue involvement. In non-culture verified studies, 6% – 12% of lesions seen on MRI were not visible on radiographs.^5,17,56,57 Jain noted in 49 cases of STB that, when investigated radiographically, the average number of involved vertebra reported was 2.6, compared to 3.2 on MRI investigations.^{5,18,23,56,57} However, in poor resource settings, MRI is often not available and therefore careful interpretation of radiograph findings is essential, especially as many of the differential conditions are difficult to differentiate from STB even on MRI.²⁴

Interpreting radiograph findings: At the earliest stages of STB, radiographs may show no changes. With disease progression, lesions may be seen in the following patterns: paradiscal, anterior, central and posterior (Box 1⁵⁹; Figure 1). The presence of calcification within an abscess is considered diagnostic of STB.²⁰

Importantly, radiographs can reveal spinal instability when they are evaluated using Rajasekaran’s ‘spine at risk’ signs (Figure 2).⁶¹

Telemedicine support for interpretation of radiographic investigations: Telemedicine support has been very effective in ophthalmology, with the Vula App assisting clinicians in remote areas to interpret test results and optimise diagnosis.⁶² Increased telemedicine support, in the form of assisting in reading radiographs of patients who have suspected STB, may enable earlier diagnosis of STB and increase the skills of primary care clinicians.

District hospitals may have access to ultrasound, a cost-effective imaging modality. An abdominal ultrasound performed by an experienced clinician or ultrasonographer could assist in the exploration of extra-pulmonary TB (EPTB) sites or lymph nodes that can be found concomitantly with STB.^11,17,20,29 STB, as a form of EPTB, can be accompanied by other forms of EPTB. If EPTB sites are identified and positively diagnosed using ultrasound, the likelihood of STB as a cause for back pain is increased. Further, given that treatment of EPTB is of the same duration as STB, the dual diagnosis ensures a patient with query STB receives adequate treatment. In the presence of accessible abscesses, ultrasound can guide a percutaneous biopsy, which can then be sent for culture and assessed with GeneXpert.^11,18,29 Held et al., in their study comparing culture and GeneXpert in 71 biopsy samples, recently evaluated GeneXpert to have the following accuracies: sensitivity 95.6%, specificity 96.2%, positive predictive value 97.7% and negative predictive value 92.6%. The speed of reporting is a major advantage of GeneXpert.^6,63,64 It should be noted that routine drainage of abscesses is not recommended, as this may result in sinus formation.^20,65,66

In patients living with HIV whose CD4 count is <200, the newly available urine Lipoarabinomannan (LAM) test is a useful adjunct to the diagnosis of TB with a positive predictive value of 88.5% and a negative predictive value of 87.1% for all TB when used alone.⁴³ Therefore, it is not specific for STB but can be a useful adjunct to diagnosis, specifically in patients whose CD4 count is < 200.