Tuberculosis (extrapulmonary and latent): Clinical sciences

Latent tuberculosis or TB refers to an asymptomatic condition where Mycobacterium tuberculosis is present in the body but held in check by the immune system.

On the other hand, extrapulmonary TB occurs when Mycobacterium tuberculosis affects organs other than the lungs. Depending on the affected organs, extrapulmonary TB can be subdivided into tuberculous lymphadenitis, pleural TB, spinal TB, tuberculosis peritonitis, as well as tuberculosis meningitis, and genitourinary TB.

Okay, so if a patient presents with risk factors for tuberculosis, first perform a focused history and physical exam. History may reveal risk factors for TB exposure, like living in densely populated areas, like residents of a homeless shelter, correctional facility, or nursing home. Your patient might also be a healthcare worker with exposure to a patient with TB; a family member or close contact of a person with TB; or a traveler to a country with a high prevalence of TB.

Additionally, the patient may have risk factors for developing TB disease, such as being immunocompromised due to HIV, malignancy, or treatment with immunosuppressive therapy. They could also have a history of latent TB.

Okay, once you identify risk factors for tuberculosis, your next step is to assess for signs and symptoms of tuberculosis disease. These signs and symptoms typically include fever, night sweats, and chronic cough, which can be associated with purulent sputum or hemoptysis. They might also have unintentional weight loss, and general body weakness.

If these signs and symptoms are absent, suspect latent tuberculosis infection. Your next step here is to check an interferon-gamma release assay or IGRA, also known as QuantiFERON-TB Gold, or a tuberculin skin test.

Now, here’s a high-yield fact! The tuberculin skin test can produce false positives in individuals exposed to non-tuberculous mycobacteria, or those vaccinated with the BCG vaccine. For this reason, serum assays like the interferon-gamma release test are more specific for Mycobacterium tuberculosis. However, none of these tests can differentiate latent infection from active disease.

Let’s take a look at the result of the tests. If the interferon-gamma release assay or a tuberculin skin test is negative, then the patient does not have latent TB infection, so you should consider an alternative diagnosis. On the other hand, if the test is positive, order a chest x-ray to rule out pulmonary tuberculosis. If the chest x-ray shows consolidation, cavitation in the upper lobes, or nodular opacities suspect pulmonary TB.

To confirm, order sputum nucleic acid amplification testing, or NAAT; as well as a smear for acid fast bacilli or AFB; and consider mycobacterial culture. If the results are positive, diagnose pulmonary tuberculosis and start your patient on RIPE therapy, which stands for rifampin, isoniazid, pyrazinamide, and ethambutol. RIPE therapy is given for 2 months, after which the patient should take isoniazid and rifampin for at least 4 months.

On the flip side, if the chest x-ray has no signs of pulmonary TB, diagnose latent tuberculosis infection. In this case, you can start treatment with one of the following; rifampin daily for 4 months, isoniazid plus rifapentine weekly for 3 months, isoniazid plus rifampin daily for 3 months, or isoniazid monotherapy daily or twice weekly for 6 to 9 months. Short-course treatment regimens are effective, safe, and have higher completion rates than longer ones, while a rifampin-based regimen is preferred due to its lower risk of hepatotoxicity than isoniazid monotherapy.

Okay, now let’s go all the way back and discuss patients that present with signs and symptoms of tuberculosis disease. At this point, you should suspect active tuberculosis disease, so your next step is to assess which organs are involved.

Let’s start with tuberculous lymphadenitis! These patients present with chronic, often bilateral, non-tender cervical lymphadenopathy. They may also have a history of fever, night sweats, and unintentional weight loss.

Physical exam reveals discrete, firm, and non-tender lymph nodes. In this case, suspect tuberculous lymphadenitis, which is the most common form of extrapulmonary tuberculosis. Of note, tuberculous lymphadenitis in the cervical region is known as scrofula.

Here’s a clinical pearl! In non-endemic countries, most patients with tuberculous lymphadenitis have no evidence of active pulmonary TB on chest radiographs. Neck imaging modalities include ultrasonography, CT, and MRI.

Next is tuberculous pleural effusion. In this case, your patient will typically report cough and pleuritic chest pain, while their physical exam reveals dullness to percussion and diminished breath sounds on auscultation.

Your next step is to obtain a chest x-ray or CT scan. If you find unilateral pleural effusion and pleural thickening, perform a diagnostic thoracentesis. Exudative effusion with an elevated white blood cell count with a lymphocyte predominance, and elevated pleural fluid adenosine deaminase or ADA should make you suspect tuberculous pleural effusion.

Okay, next up is spinal tuberculosis! Consider the possibility of spinal tuberculosis if your patient has a history of back pain and muscle spasms. Physical exam typically reveals tenderness to palpation of the spine, spinal deformity, and neurologic deficits at the level of the deformity.