PANCE Blueprint Pulmonary (10%)

Tuberculosis (ReelDx + Lecture)



8-year-old with 3 months of cough, night sweats, and arthritis

Patient will present as → a 78-year-old man with a 3-month history of weight loss, fever, fatigue, night sweats, and cough. He is a former smoker. A recent HIV test was negative. A CT scan of the chest reveals a 3 cm lesion in the upper lobe of the left lung and calcification around the left lung hilus. A sputum smear was positive for acid-fast organisms. 

Organism: Mycobacterium tuberculosis: transmitted by respiratory droplets

  • Classic findings include fever, night sweats, anorexia, and weight loss

 Screening/testing (CDC guidelines)

There are two kinds of tests that are used to detect TB bacteria in the body: the TB skin test (TST) and TB blood tests (IGRAs)

  • A positive TST or IGRA only tells that a person has been infected with TB bacteria. It does not tell whether the person has latent TB infection (LTBI) or has progressed to TB disease
  • IGRAs are the preferred method of TB testing for people who have received the BCG vaccine and those who may have a difficult time returning for a second appointment to have a TST read
  • The TB skin test is the preferred TB test for children under the age of five

PPD Rules: Area of induration = raised area (not the red area). Positive if:

  • > 5 mm: Patients at high risk of developing active TB if infected, such as those who have chest x-ray evidence of past TB, who are immunosuppressed because of HIV infection or drugs (eg, TNF-α inhibitors, corticosteroid use equivalent to prednisone 15 mg/day for > 1 mo), or who are close contacts of patients with infectious TB.
  • > 10 mm: Patients with some risk factors, such as injection drug users, recent immigrants from high-prevalence areas, residents of high-risk settings (eg, prisons, homeless shelters), patients with certain disorders (eg, silicosis, renal insufficiency, diabetes, head or neck cancer), and those who have had gastrectomy or jejunoileal bypass surgery.
  • > 15 mm: Patients with no risk factors

All persons with either symptoms or a positive TB test (TST or IGRA) result should be evaluated for TB disease. If a person has symptoms, but a negative TB test result, they should still be evaluated for TB disease

Diagnose TB with sputum for AFB smears and cultures

  • Isolate hospitalized patients who may have TB (cough for 3 weeks, night sweats, hemoptysis, etc.) and send three sputum specimens for acid-fast bacilli staining (AFB smears) and Mycobacterium tuberculosis cultures  

Xray: upper cavitary lesions, infiltrates, ghon complexes in the apex of lungs

  • Ghon complex (calcified lymph + lesions)
  • Biopsy: Caseating granulomas

Miliary Tb (Tb spread outside the lungs)

  • Potts DZ - Tb to spine
  • Scrofula - Tb to cervical lymph nodes

If PPD/IGRA is + order a CXR

  • If CXR negative - Latent TB treat with Isoniazid for 9 months
  • Pt's on INH should take supplemental Vitamin B6 (Pyridoxine) daily to prevent neuropathy

Active treatment: quad therapy (RIPE): Rifampin, Isoniazid, Pyrazinamide, Ethambutol. All are Hepatotoxic so you need to get baseline labs

Four drugs x 8 weeks then two drugs x 16 weeks

  • Rifampin (RIF): Orange body fluids, hepatitis - "remember R = red/orange body fluids"
  • Isoniazid (INH): peripheral neuropathy (give with B6- pyridoxine 25 to 50 mg/day)
  • Pyrazinamide (PZA): Hyperuricemia (Gout)
  • Ethambutol (EMB): Optic neuritis, red-green blindness - "remember E = eyes"
Did you know that patients need to be tested for tuberculosis prior to being treated with etanercept (Enbrel). Etanercept is an anti-cytokine agent used in the treatment of rheumatoid arthritis and has as a side effect the potential for serious infections. One of these side effects includes the reactivation of dormant tuberculosis."

Most outpatients will be managed by your local health department to directly observe them taking TB meds, for monitoring, etc.

  • Patients with active TB will need two negative AFB smears and cultures in a row negative for therapy cessation
  • Prophylaxis for household members: Isoniazid for 1 year

Treatment Summary

  • We know to isolate hospitalized patients who may have TB (cough for 3 weeks, night sweats, hemoptysis, etc)...and send three sputum specimens for acid-fast bacilli and Mycobacterium tuberculosis cultures.  
  • Also order a newer test called nucleic acid amplification. It is better at identifying TB versus other forms of Mycobacterium...can help detect possible TB sooner...and help get patients out of isolation earlier.
  • Start empiric treatment in those likely to have TB...such as a symptomatic patient with TB exposure. Use culture results to confirm the diagnosis...these are usually available within 6 weeks.
  • Continue to treat most patients for 2 months with isoniazid, rifampin, ethambutol, and pyrazinamide...followed by an additional 4 months of just isoniazid and rifampin.
  • Monitor serum creatinine and adjust dosing, if needed. For example, reduce ethambutol and pyrazinamide dosing to three times per week instead of daily in patients with a CrCl of less than 30 mL/min.
  • Add pyridoxine 25 to 50 mg/day when isoniazid is used in patients at risk for neuropathy...such as those with alcoholism, diabetes, or HIV.
  • Most outpatients will be managed by your local health directly observe them taking TB meds, for monitoring, etc.
  • Reinforce ways to improve med efficacy in your office...such as advising to take most TB meds on an empty stomach, since food can reduce absorption. If patients complain of nausea, try adding an antacid.
  • Watch for hepatotoxicity with isoniazid, pyrazinamide, or rifampin...and severe side effects such as rash, drug fever, etc.
  • Also be aware of drug interactions...especially with HIV meds. For example, double the raltegravir (Isentress) dose when used with rifampin.

osmosis Osmosis


Tuberculosis is caused by Mycobacterium tuberculosis and is the leading cause of death worldwide from an infectious bacterial disease. Mycobacterium are noted for having mycolic acid cell walls, which make them acid fast and stain to carbolfuchsin red. Cell smears from colonies have a distinctive look that resembles serpentine cords. Primary tuberculosis is the form of disease that occurs in a previously unexposed person. Most people do not develop clinically significant disease. The inhaled bacillus implants in the lower part of the upper lobe and can cause a focus of inflammation and consolidation called a ghon focus. The bacilli can drain to regional lymph nodes and the combination of a ghon focus with perihilar lobar lymph nodes constitutes a ghon complex. Secondary tuberculosis occurs in previously exposed people via reactivation of a latent infection but can also occur from a new exposure in the immunocompromised. Secondary pulmonary tuberculosis typically involves the apex of the upper lobes because the upper regions of the lungs are well-aerated where the bacteria thrive. Systemic symptoms commonly include fever, weight loss and night sweats. Many patients also present with hemoptysis. Tuberculosis can spread beyond the lungs when the bacteria disseminate through the systemic arterial system. Common organs involved include the adrenal glands, CNS, GI, liver, vertebrate, kidneys, and bone.

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Tuberculosis Skin Mantoux Test (PPD)


Mantoux test using purified protein derivative (PPD)  is performed as a standard screening test for tuberculosis (TB). Memory cells generated during the body’s initial cell-mediated response to TB will react to the PPD intradermal injection, creating a delayed hypersensitivity reaction and a positive TB skin test. The results of the skin test must be interpreted by a nurse within 48 to 72 hours of receiving the PPD injection and are invalid when read before or after the allotted time frame. A positive test result will appear as an induration or a hardened mass, which is then measured to determine if the patient has tested positive or negative. Patients who test positive for TB should also get a chest x-ray to confirm or substantiate the diagnosis.

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Ethambutol is a bacteriostatic antimycobacterial drug used in the treatment of tuberculosis. It is often given in combination with isoniazid, rifampin, and pyrazinamide for treatment of active TB. This drug works by blocking bacterial arabinosyl transferase enzyme, which polymerizes carbohydrates in the bacterial cell wall. Disruption of this bacterial enzyme therefore leads to increased permeability of the cell wall. This drug can be especially toxic to the eyes, with adverse effects of optic neuritis and red-green color blindness reported.

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Isoniazid is a drug used in the treatment of both latent and active tuberculosis. It can be used as a monotherapy for the treatment of latent tuberculosis but is commonly used in a four-drug regimen including pyrazinamide, ethambutol, rifampin for active TB. Isoniazid is a pro-drug and requires bacterial catalase-peroxidase enzyme to activate it and works by inhibiting the synthesis of mycolic acid. It is metabolized in the liver via acetylation. There are two forms of the acetylating enzyme, a fast acetylator and a slow acetylator. Those with the fast acetylator metabolize the drug more quickly than the slow acetylators. Common side effects include vitamin B6 deficiency, hepatotoxicity and neurotoxicity. Isoniazid is also associated with drug induced lupus erythematosus.

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Rifampin, also called rifampicin, is a bactericidal antibiotic commonly used in the treatment of active tuberculosis. Rifampin inhibits bacterial RNA synthesis by inhibiting RNA polymerase. Rifampin resistance can develop quickly due to alteration of the binding sites on RNA polymerase so monotherapy should not be used in treatment of infections. Instead, rifampin is commonly used in combination with other antibiotics. Besides mycobacterium TB, rifampin is also used in the treatment of haemophilus influenza, leprosy, and meningitis. Rifampin is a well known P450 inducer and can increase the rate of metabolism of other drugs that are cleared by the liver through the p450 system. Taking rifampin can cause bodily fluids like urine and tears to become orange red in color, which may be alarming but is completely benign.

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Question 1
An adult patient who is HIV positive receives a PPD. He develops an area of induration that measures 8 mm after 48 hours. Which of the following is the most appropriate interpretation of this test result?
See A for explanation.
active infection
A positive PPD identifies patients that have been infected with Mycobacterium tuberculosis, but does not indicate whether the disease is currently active or inactive.
falsely negative
See A for explanation.
Question 1 Explanation: 
A reaction size of greater than or equal to 5 mm in a HIV positive patient is considered a positive tuberculin skin test reaction.
Question 2
Which of the following is the greatest risk factor for the development of drug resistance in the treatment of tuberculosis?
A child with cystic fibrosis
Children with cystic fibrosis are at an increased risk for various lung infections, but not drug resistance.
An elderly patient in a nursing home
While institutionalized patients, such as nursing home residents, are at increased risk for infection with Mycobacterium tuberculosis, the patient is not at increased risk for drug resistance.
Non-adherence to prescribed drug regimen
Patients with a history of diabetes mellitus
Patients with a history of diabetes mellitus are at increased risk for active disease, not drug resistance.
Question 2 Explanation: 
Non-adherence to prescribed drug regimens is a risk factor for the development of drug resistance as well as being a major cause of treatment failure and continued transmission of tuberculosis. Patient education about the importance of drug therapy is important in an attempt to avoid this.
Question 3
A patient should be tested for tuberculosis prior to being treated with
etanercept (Enbrel).
cyclosporine (Neoral).
Cyclosporine, methotrexate, and prednisone do not have the requirement to check for tuberculosis prior to initiating treatment.
methotrexate (Rheumatrex).
See B for explanation.
prednisone (Deltasone).
See B for explanation.
Question 3 Explanation: 
Etanercept is an anti-cytokine agent used in the treatment of rheumatoid arthritis and has as a side effect the potential for serious infections. One of these side effects includes reactivation of dormant tuberculosis.
Question 4
A 62 year-old homeless patient presents complaining of fever, weight loss, anorexia, night sweats and a chronic cough that recently became productive of purulent sputum that is blood streaked. On physical examination, the patient appears chronically ill and malnourished. Which of the following chest x-ray findings supports your suspected diagnosis?
Hyperinflation and flat diaphragms
Chest x-ray findings of hyperinflation and flat diaphragms suggest long-standing chronic obstructive lung disease.
Interstitial fibrosis and pleural thickening
Interstitial fibrosis and pleural thickening on a chest x-ray are found in cases of interstitial lung disease.
Cavitary lesions involving the upper lobes
"Eggshell" calcification of hilar lymph nodes
Chest x-ray findings of "eggshell" calcification of hilar lymph nodes strongly supports a diagnosis of silicosis.
Question 4 Explanation: 
This patient most likely has tuberculosis. A chest x-ray finding of cavitary lesions involving the upper lobes would support this suspected diagnosis.
Question 5
A 33 year-old HIV-positive woman develops an 8mm area of induration following the administration of a purified protein derivative (PPD) test. Her chest radiograph shows no evidence of active tuberculosis (TB) infection. Which of the following is the most appropriate clinical intervention?
Four-drug regimen for 4 months
Greater than 5 mm of induration is positive in an HIV-infected patient. A positive PPD and negative chest film is considered latent TB infection and, while requiring treatment, does not require the full four-drug regimen.
Isoniazid with Rifampin
Observation only
Latent TB infection is associated with a risk of progression to tuberculosis and observation alone is inadequate.
Repeat PPD and chest radiograph in 3 months
Repeat screening is not helpful since the diagnosis of latent TB infection has already been established.
Question 5 Explanation: 
isoniazid with Rifampin is recommended in HIV positive patients with a positive PPD and a negative chest x- ray.
Question 6
A recent Haitian immigrant presents to the clinic for an employment physical examination before starting work at a local hospital. The patient has a history of receiving bacilli Calmette-Guerin (BCG) vaccination. Screening for tuberculosis for this employee should include which of the following tests?
Sputum induction
Sputum induction should not be used as a screening test for tuberculosis.
PPD skin test
See E for explanation
Chest x-ray
A chest X-Ray will need to be performed if this patient's initial screening is positive. In this case >10 mm TST or a + IGRA
No screening needed
This patient has recently emigrated from a possible endemic region and should be screened for tuberculosis.
TB blood test (IGRA)
Question 6 Explanation: 
TB screening is recommended for all healthcare personnel, including a symptom evaluation and test (IGRA or TST) for those without documented prior TB disease or LTBI. TB blood tests (IGRAs) are preferred for most non-United States-born patients who received (or may have received) BCG vaccination. IGRAs, unlike the TB skin test, are not affected by prior BCG vaccination and are not expected to give a false-positive result in people who have received BCG. The TST is an acceptable alternative to IGRA, especially in situations where IGRA is not available or is too costly (even though it is less specific than the IGRA). In this case > 10mm would be positive and will require a follow-up CXR.
There are 6 questions to complete.
Shaded items are complete.

References: Merck Manual · UpToDate

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