Tuberculosis (extrapulmonary and latent): Clinical sciences

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Introduction0:00–0:41

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 & Physical0:41–1:29

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.

Assess for Signs/Symptoms1:29–1:54

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.

Absent Signs/Symptoms1:54–2:41

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.

Pulmonary TB2:41–3:51

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.

Latent TB3:51–4:34

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.

Signs/Symptoms Present4:34–4:51

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.

Tuberculous lymphadenitis4:51–5:41

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.

Tuberculous Pleural Effusion5:41–6:24

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.

Spinal tuberculosis6:24–7:07

Physical exam typically reveals tenderness to palpation of the spine, spinal deformity, and neurologic deficits at the level of the deformity.
You should then order an MRI of the spine, and if it reveals destruction of two adjacent vertebral bodies and the intervening disc, with or without an adjacent abscess, suspect spinal tuberculosis, also known as Pott disease.
Of note, other forms of skeletal TB include osteomyelitis and arthritis. Moving on to tuberculous peritonitis!

Tuberculous peritonitis7:07–8:06

These individuals typically present with abdominal pain, and may have a history of cirrhosis or end-stage renal disease or ESRD on peritoneal dialysis.
Physical exam reveals a distended abdomen that’s tender to palpation. Next, order a CT abdomen, which usually reveals a thickened peritoneum, ascites, and enlarged mesenteric lymph nodes.
Next, perform a diagnostic paracentesis and order ascitic fluid analysis. If it shows a serum ascites albumin gradient lower than 1.1 grams per deciliter with an ascitic fluid protein level >2.5g/dL, low glucose concentration, and an elevated white blood cell count with lymphocytic predominance, suspect tuberculous peritonitis.
Next is tuberculous pericarditis! Patients typically report chest pain, cough, and dyspnea; while physical exam reveals jugular venous distention, hepatomegaly, and a pericardial rub.

Tuberculous Pericarditis8:06–8:50

In this case, you should obtain a transthoracic echocardiogram, which will likely show a pericardial effusion. Next, perform a diagnostic pericardiocentesis.
If the pericardial fluid analysis reveals an exudate with high protein levels and elevated white blood cell count with lymphocytic predominance, suspect tuberculous pericarditis.
Ok, next up is tuberculous meningitis! Let’s say your patient reports malaise, headache, vomiting, confusion, and in some cases, even seizures.

Tuberculous meningitis8:50–9:48

Additionally, if their physical exam reveals nuchal rigidity, and focal neurologic deficits, such as cranial nerve palsy or hemiparesis, you should suspect central nervous system involvement.
In this case, order a head CT and CSF analysis. The CT may show basilar arachnoiditis, hydrocephalus, or tuberculomas, whereas CSF analysis will reveal an elevated white blood cell count with lymphocytic predominance.
With these findings, you should suspect tuberculous meningitis.Here’s a clinical pearl! Adjunctive corticosteroids like dexamethasone or prednisolone can help reduce the risk of death or disabling residual neurologic deficits.
Finally, let’s go over genitourinary tuberculosis! These patients typically report symptoms of urinary infection, such as urinary frequency, difficulty voiding, blood in the urine, and abdominal or suprapubic pain.

Genitourinary tuberculosis9:48–11:12

First, check urinalysis and urine culture. Urinalysis will typically reveal hematuria, sterile pyuria, positive leukocyte esterase, and negative bacteriuria.
Additionally, urine cultures will be negative! Next, order imaging like a CT or CT urogram, which will help you identify granulomas in the kidney, as well ureteral or bladder wall thickening with calcifications.
In this case, suspect genitourinary tuberculosis. Here’s a high-yield fact!
Miliary TB is an aggressive, disseminated form of extrapulmonary TB associated with systemic symptoms like fever, anorexia, and weight loss, as well as localized symptoms, depending on which organ systems are involved, and can cause multiple-organ failure.
Evaluation includes a dilated funduscopic examination, since choroidal tubercles are characteristic and, if present, strongly support the diagnosis of miliary TB.
Okay, no matter what type of extrapulmonary tuberculosis you suspect, your next step is to order further diagnostic tests.

Extrapulmonary Tuberculosis11:12–12:10

Send fluid and tissue samples for Mycobacterium tuberculosis culture. Keep in mind that culture results can take weeks to return, so you should also perform more rapid tests, such as NAAT and AFB!
There are also other supportive tests, such as ADA and interferon-gamma or IFN-gamma levels in CSF or in pleural, peritoneal, or pericardial fluid.If the culture returns positive for Mycobacterium tuberculosis, you can diagnose extrapulmonary TB.
Positive NAAT and AFB are supportive of diagnosis, but remember that negative results don’t rule out TB. Similarly, if ADA and interferon-gamma levels are elevated, tuberculosis is more likely, but don’t rely on these tests to definitively diagnose extrapulmonary TB!Once you diagnose the patient with extrapulmonary tuberculosis, you should perform drug susceptibility testing.
If results show no drug resistance, the patient can start RIPE therapy for 2 months and then switch to rifampin and isoniazid for another 4 months.

Drug Susceptibility Testing12:10–13:26

Keep in mind that patients with tuberculous meningitis and spinal TB require longer therapeutic regimens. On the other hand, if testing reveals drug-resistant tuberculosis, assess what drug is affected.
If there’s isoniazid-resistant TB, meaning the pathogen is only resistant to isoniazid, you can replace it in RIPE with a fluoroquinolone, and treat it for 6 months.
On the flip side, if there’s rifampin-resistant- or multi-drug-resistant TB, meaning respectively that the pathogen is resistant to rifampin, or to both isoniazid and rifampin, you should start your patient on bedaquiline, pretomanid, linezolid, and moxifloxacin for 6 months.
Finally, if testing reveals extensively drug-resistant TB, you should tailor therapy based on susceptibility for a prolonged treatment course.
Alright, as a quick recap... If your patient has risk factors for TB, assess them for possible signs and symptoms.
If absent, test for latent TB infection using interferon-gamma release assays or tuberculin skin testing. Treat positive latent TB infection to reduce the risk of developing active tuberculosis disease.
On the other hand, if signs and symptoms are present, suspect active tuberculosis disease. If you suspect extrapulmonary TB, collect fluid or tissue samples from the affected organ system and send for mycobacterial culture.

Review13:26–14:09

If the culture is positive, test for drug susceptibility and treat based on the results. reduce the risk of developing active tuberculosis disease On the other hand if signs and symptoms are present suspect active tuberculosis disease if you suspect extrapulmonary TB collect fluid or tissue samples from the affected organ system and send for mycobacterial culture If the culture is positive test for drug susceptibility and treat based on