Diagnostics: Extrapulmonary TB

/

Tuberculosis is often thought of as a pulmonary disease, however, Mycobacterium tuberculosis can spread throughout the entire body, causing extrapulmonary tuberculosis (EPTB). EPTB can present with a wide variety of symptoms, often in the absence of any respiratory symptoms. The manifestations of extrapulmonary TB are often indolent and slow to progress, making diagnosis difficult.  Delayed diagnoses of EPTB can result in significant morbidity, mortality, and further spread of the disease, making it important for emergency medicine physicians to be aware of what its presentation may look like. This article will review how EPTB is spread, who is at greatest risk, management within the ED, as well as the most common presentations.

Quick Facts

  • EPTB, like pulmonary TB, is acquired via inhalation of respiratory droplets infected with M. tuberculosis

  • The bacteria then spread from the lungs systemically via the lymphatic or circulatory systems - this can occur with or without pulmonary infection

  • Patients with isolated EPTB are generally considered non-infectious, but should still be placed in respiratory precautions

    • Up to 45% of EPTB cases have a concomitant pulmonary component

    • 13% of patients with EPTB and a negative chest X-ray have positive sputum cultures, indicating active infectious disease

Risk Factors:

Below are the most common risk factors associated with increased odds of EPTB. Patients with these risk factors should have an increased suspicion for extrapulmonary TB, especially when multiple are present.

  • HIV infection

    • Odds ratio (OR): 4.93–16.3

    • Risk increases with lower CD4 counts, especially <200 cells/µL

  • Female sex

    • OR: 1.6–1.98

    • Persistent across geographic regions and independent of other risk factors

  • Age

    • Children <15 years: OR 5.50

      • Primarily lymphatic and CNS disease

    • Adults >45 years

      • Higher rates of bone and joint TB

  • Foreign birth

    • Most prominent from the Indian subcontinent, Africa, and Southeast Asia

    • Region of origin may influence disease manifestation

  • Prior TB infection or known TB exposure

  • End-stage renal disease

  • Immunosuppression

    • Chronic steroid use

    • TNF-alpha inhibitors

    • Solid organ transplant

    • Other immunosuppressive medications

Management in the ED

  • Place the patient in a negative-pressure room with airborne precautions

    • Isolation should not be delayed while awaiting imaging

  • Obtain baseline testing:

    • Chest X-ray

    • AFB smear and culture (sputum induction may be required)

    • NAAT testing

    • HIV testing

  • Additional workup should be guided by the individual complaint will be covered below

MOST COMMON PRESENTATIONS

Tuberculous Lymphadenitis

  • Presentation

    • Painless, fluctuant, unilateral lymph node enlargement

    • Most commonly involves cervical lymph nodes

    • May progress to ulceration, fistula, or abscess formation

    • Symptoms may be present for up to 12 months prior to diagnosis

    • Constitutional symptoms (fever, weight loss, night sweats) are often absent

  • Diagnosis

    • Fine-needle aspiration or excisional lymph node biopsy is required for definitive diagnosis

  • Treatment

    • 2 months of RIPE therapy (rifampin, isoniazid, pyrazinamide, and ethambutol) followed by 4 months of rifampin and isoniazid

    • Temporary enlargement or appearance of new lymph nodes may occur during treatment before improvement

Pleural Tuberculosis

  • Presentation

    • Pleuritic chest pain, nonproductive cough, and fever

    • May also include night sweats, weight loss, dyspnea, and weakness

    • Can progress to tuberculous empyema

  • Diagnosis

    • Chest X-ray typically show a  small-to-moderate unilateral pleural effusion

    • Thoracentesis with pleural fluid analysis:

      • Elevated LDH (often >500 IU/L)

      • pH <7.4

      • Glucose 60–100 mg/dL

      • Nucleated cell count 1,000–6,000 cells/mm³

        • Lymphocyte-to-neutrophil ratio >0.75

      • Adenosine deaminase (ADA) >40 units/L

  • Treatment

    • Standard RIPE therapy (2 months) followed by rifampin and isoniazid (4 months)

    • Pleural drainage may be considered for symptomatic dyspnea

Bone and Joint Tuberculosis

  • Presentation

    • Pott disease (spinal TB)

      • Progressive localized back pain

      • Commonly affects lower thoracic and upper lumbar spine

      • Gait changes and postural abnormalities may be present

      • Fever and weight loss are uncommon

    • Tuberculous arthritis

      • Monoarticular swelling, pain, and loss of function

      • Most commonly affects the hip and knee

      • Erythema and warmth of joint are usually absent

    • Osteomyelitis

      • “Cold abscess” with swelling, mild pain, and minimal erythema

        • No warmth over the area

      • Typically affects a single bone

  • Diagnosis

    • Definitively diagnosed by microscopy and culture of infected tissue

    • No pathognomonic imaging findings on MRI or CT

  • Treatment

    • Standard RIPE therapy (2 months) followed by rifampin and isoniazid (4 months)

    • Surgery is often only considered in spinal TB with  spinal instability, neurologic compromise, kyphosis, or treatment failure

  • Important Note

    • Chronic back pain with new neurologic deficits warrants urgent imaging and specialist consultation

Genitourinary Tuberculosis

  • Presentation

    • Renal and urologic TB

      • Initially asymptomatic with sterile pyuria or microscopic hematuria

      • Progresses to dysuria, urgency, and frequency

    • Male genital TB

      • Testicular swelling, scrotal nodules, or epididymal hardening

      • Bilateral involvement in up to one-third of cases

    • Female genital TB

      • Infertility, abdominal/pelvic pain, menstrual irregularities

      • Commonly affects fallopian tubes

  • Diagnosis

    • CT urography for renal/urologic disease

    • Biopsy of affected tissue for definitive diagnosis in genital TB

    • Hysterosalpingogram may aid diagnosis in female genital TB by showing fallopian tube  obstruction  or uterus deformities

  • Treatment

    • Standard RIPE therapy (2 months) followed by rifampin and isoniazid (4 months)

    • Stenting or nephrostomy tubes for obstructive uropathy

MRI or CT to identify intracranial lesions (Case courtesy of Mohammad Mujalli, <a href="https://radiopaedia.org/?lang=us">Radiopaedia.org</a>. From the case <a href="https://radiopaedia.org/cases/84994?lang=us">rID: 84994</a>) use by CC - SA 3.0

Tuberculous Meningitis

  • Presentation

    • Headache, fever, neck stiffness, vomiting

    • Distinguishing features from bacterial meningitis:

      • Subacute presentation

      • Cranial nerve palsies

      • Altered mental status

  • Diagnosis

    • CSF NAAT, AFB smear, or mycobacterial culture

    • CSF findings:

  • Lymphocytic pleocytosis

  • Elevated protein

  • Low glucose

  • MRI or CT to identify intracranial lesions (see attached)

  • Treatment

    • RIPE therapy for 2 months, followed by 7–10 months of rifampin and isoniazid

    • Dexamethasone or prednisone  for 6–8 weeks

Peritoneal, omental, and mesenteric thickening (Case courtesy of Mohammad Mujalli, <a href="https://radiopaedia.org/?lang=us">Radiopaedia.org</a>. From the case <a href="https://radiopaedia.org/cases/84994?lang=us">rID: 84994</a>) use by CC - SA 3.0

Peritoneal Tuberculosis

  • Presentation

    • Ascites, abdominal pain, fever

    • Advanced disease may present with minimal distension (“dry” phase)

  • Diagnosis

    • Definitively diagnosed by peritoneal fluid or tissue biopsy

    • Ascitic fluid analysis:

  • Lymphocytic predominance

  • Serum–ascites albumin gradient <1.1 g/dL

  • ADA >30 units/L

  • CT findings:

    • Ascites (red arrow)

    • Abdominal lymphadenopathy (green arrow)

    • Peritoneal, omental, and mesenteric thickening (Case courtesy of Mohammad Mujalli, <a href="https://radiopaedia.org/?lang=us">Radiopaedia.org</a>. From the case <a href="https://radiopaedia.org/cases/84994?lang=us">rID: 84994</a>)

  • Treatment

    • Standard RIPE therapy (2 months) followed by rifampin and isoniazid (4 months)

Key Takeaways for the Emergency Department

  • Extrapulmonary TB often presents without pulmonary symptoms but still needs respiratory negative pressure precautions initially

  • Maintain suspicion in high-risk populations with subacute or chronic complaints

  • Isolate early and test broadly

  • A normal chest X-ray does not rule out TB or infectiousness

References

  1. Shivakumar SVBY, Padmapriyadarsini C, Chavan A, et al. Concomitant pulmonary disease is common among patients with extrapulmonary TB. Int J Tuberc Lung Dis. 2022;26(4):341-347. doi:10.5588/ijtld.21.0501

  2. Le V, Pascopella L, Westenhouse J, Barry P. A Cross-sectional Study of Patients With Extrapulmonary Tuberculosis and Normal Chest Radiographs - What Characteristics Were Associated With Sputum Culture Positivity?. Clin Infect Dis. 2022;75(12):2113-2118. doi:10.1093/cid/ciac338

  3. Peto HM, Pratt RH, Harrington TA, LoBue PA, Armstrong LR. Epidemiology of extrapulmonary tuberculosis in the United States, 1993-2006. Clin Infect Dis. 2009;49(9):1350-1357. doi:10.1086/605559

  4. Wang S. Tuberculous lymphadenitis. In: Post TW, ed. UpToDate. UpToDate; 2026. Accessed February 18, 2026. https://www.uptodate.com/contents/tuberculous-lymphadenitis

  5. Head lymph. Public Domain Media Search Engine. Accessed March 1, 2026. https://garystockbridge617.getarchive.net/amp/media/head-lymph-83d93b 

  6. Chopra A, Huggins JT, Hu K. Tuberculous pleural effusion. In: Post TW, ed. UpToDate. UpToDate; 2026. Accessed February 18, 2026. https://www.uptodate.com/contents/tuberculous-pleural-effusion

  7. Visweswaran RK, Pais VM, Dionne J. Urogenital tuberculosis. In: Post TW, ed. UpToDate. UpToDate; 2026. Accessed February 18, 2026. https://www.uptodate.com/contents/urogenital-tuberculosis

  8. Stout, J. Bone and joint tuberculosis. In: Post TW, ed. UpToDate. UpToDate; 2026. Accessed February 18, 2026. https://www.uptodate.com/contents/bone-and-joint-tuberculosis

  9. Ahuja V. Abdominal tuberculosis. In: Post TW, ed. UpToDate. UpToDate; 2026. Accessed February 18, 2026. https://www.uptodate.com/contents/abdominal-tuberculosis

  10. Garg RK. Central nervous system tuberculosis: An overview. In: Post TW, ed. UpToDate. UpToDate; 2026. Accessed February 18, 2026. https://www.uptodate.com/contents/central-nervous-system-tuberculosis-an-overview

  11. Garg RK. Central nervous system tuberculosis: Treatment and prognosis. In: Post TW, ed. UpToDate. UpToDate; 2026. Accessed February 18, 2026. https://www.uptodate.com/contents/central-nervous-system-tuberculosis-treatment-and-prognosis

  12. Garg RK. Tuberculous meningitis: Clinical manifestations and diagnosis. In: Post TW, ed. UpToDate. UpToDate; 2026. Accessed February 18, 2026. https://www.uptodate.com/contents/tuberculous-meningitis-clinical-manifestations-and-diagnosis 

  13. Mujalli M, Tuberculosis - multisystem. Case study, Radiopaedia.org (Accessed on 01 Mar 2026) https://doi.org/10.53347/rID-84994

Post by : Tommy Schneider, MD

Dr. Schneider is a PGY-1 in Emergency Medicine at the University of CIncinnati

Editing by : Ryan LaFollette, MD

Dr. LaFollette is an APD in Emergency Medicine at the University of Cincinnati and Co-editor of Tamingthesru.com