8-year-old with 3 months of cough, night sweats, and arthritis (watch video)
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
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
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: cavitary lesions, infiltrates, ghon complexes in 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 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 (Picmonic) - "remember R = red/orange body fluids"
- Isoniazid (INH): peripheral neuropathy (give with B6- pyridoxine 25 to 50 mg/day) (Picmonic)
- Pyrazinamide (PZA): Hyperuricemia (Gout)
- Ethambutol (EMB): Optic neuritis, red-green blindness (Picmonic) - "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 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
- 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 department...to 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.
|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.|
|A 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.|
|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.|
|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.|
|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.|
See A for explanation.
A positive PPD identifies patients that have been infected with Mycobacterium tuberculosis, but does not indicate whether the disease is currently active or inactive.
See A for explanation.
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.
Cyclosporine, methotrexate, and prednisone do not have the requirement to check for tuberculosis prior to initiating treatment.
See B for explanation.
See B for explanation.
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.
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
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.
Sputum induction should not be used as a screening test for tuberculosis.
PPD skin test
False-positive tuberculin skin test reactions can occur in persons previously vaccinated against M. tuberculosis with BCG. PPD should be avoided as a screening test in these patients.
No screening needed
This patient has recently emigrated from a possible endemic region and should be screened for tuberculosis.