Tuberculosis -3 (Active TB)

Last posting (TB-2) we discussed Latent TB Infection (LTBI).  Today we’ll address specifics in the diagnosis of Active TB (termed “Disease,” as opposed to “infection”).  We focus primarily on Pulmonary TB, because it’s most common, & infectious.  Case-finding is the most important role for primary care.

CLINICAL PRESENTATION

Cough —  The cardinal symptom, no matter how minor. Suspect Active TB if:

• Cough ≥3 weeks duration that hasn’t begun to improve at all, & no other likely diagnosis (e.g. asthma, allergic rhinitis)
• Associated hemoptysis, fever, night sweats, or weight loss raise suspicion

As noted in our 1^st  posting, suspect TB especially in persons at risk for getting active TB (see TB – Overview):

• Persons Likely to be Infected with MTb
• Persons at High Risk of Active TB if Infected

WORK-UP

Chest X-Ray (CXR) is the bottom line.  A normal CXR rules out Active TB in immunocompetent patients.

• Patients with AIDS (not merely HIV) can have Active TB & a normal CXR
• In AIDS, Active TB presents with lymphadenopathy (hilar or paratracheal) instead of parenchymal lesions

Possible findings on CXR are myriad:

• Apical nodules or infiltrates are very suspicious
• Upper lobe infiltrates might be suspicious
• Cavities are highly suspicious
• Bronchogenic TB (uncommon) is highly infectious

Primary TB, i.e. active TB occurring immediately upon initial infection (as opposed to later reactivation), occurs in the debilitated & immunocompromised who can’t mount that innate immune response.  It presents just like any community acquired pneumonia, often with lobar infiltrates in lower lobes.

Remember, readings of apical / upper lobe “scar” or “old granulomatious disease” are only justified if an old comparison film confirms stability.  If the radiologist doesn’t specifically mention a prior image, consider the finding as new, active TB until proven otherwise, especially in a patient with cough.

But you can safely ignore “calcified granuloma.”  Often called “Ghon” lesions or “Rhanke” complexes, they’re burnt-out spots where TB initially entered the lungs & was transported to the hilum.  No active organisms.

Click the link for examples of TB on chest x-ray.

IMPORTANT — Active TB is merely a type of pneumonia; other microorganisms can look identical on CXR.  You need to consider the whole clinical picture.  TB is not rapidly fatal; regular Community Acquired Pneumonia often gets treated as priority target illness.

Lucky Mistake  —  an HIV patient (high risk) had been started on 4-drug TB treatment for acute fever, night sweats, & an apical infiltrate (highly suspicious for TB).  A regular blood culture had been drawn; lab called over the weekend — growth!!!  I had to get an administrator to open the clinic, find the address [no phone], and hunt the fellow down.  He was feeling better; the bug wound up Pneumococcus, & the Rifampin was working.

SPUTUMS

A suspicious CXR compatible with Active TB generates a “Sputum for AFB” exam.  Order 3 of them, each on separate days.  The first can be collected at time of initial visit (have the patient go outside to do their coughing); the next two should be early-morning specimens from home.  With a “Sputum for AFB” order, lab will perform a “smear” (direct microscopy) & “culture.”

**  Smear Results in 24 hrs.

• 50% sensitive
• Positive is treated presumptively for TB
• In AIDS, could be M. avium complex (MAC), but Tx for TB anyway pending cultures
• Negative smear awaits culture; empiric TB treatment is a judgment call

**  Nucleic Acid Amplification Testing (e.g. by PCR), rapid turnaround results

• 80% sensitive
• Expensive !!!
• Order separately on 1^st specimen only if high index of suspicion for TB

**  Culture

• 1-2 weeks by radiometric technology with DNA probe (e.g. BACTEC^®)
• Up to 60 days by conventional microbiology media
• Another 2 weeks for susceptibility results
• 98% sensitive, 100% specific

These days, all clinical labs probably employ radiometric technology for culture.  But it never hurts to ask.  I remember how, 15 years ago, I discovered our [nationally prominent] reference lab didn’t have it; I ceased ordering AFB sputums through them for the next 5 years.

“Culture-Negative TB” refers to those symptomatic smear-negative cases in which the CXR is very suspicious.  So treatment is begun, pending culture results.  The patient responds, symptoms disappear.  CXR is followed, and abnormalities resolve.  But a whole 2 months go by, cultures remain negative even on conventional media.  Still, everything looks & smells like Active TB, so Tx is continued for the entire 6-9 months.  Comprises 2% of Active TB.

Actually, all the above Dx & Tx for anyone with even intermediate-suspicion for Active TB should be done by Public Health Department TB experts.  They have the personnel resources for Directly Observed Therapy (DOT), which is mandatory.  Primary providers sometimes get possessive about their patients.  Look at it this way: if your hypertensive is non-adherent with treatment, they’ll get a stroke and die.  Alas.  But if a TB patient is non-adherent, they’ll transmit to you and me.

• Moral: Unless you’re prepared to handle daily DOT x 6-9 mos., let DPH manage active TB.

In terms of Extrapulmonary TB, symptoms often include fevers, night sweats, & weight loss.  More specific ones depend on the site (bone pain for spinal TB, swollen lymph nodes, eye pain for TB iritis, etc).  Sometimes CXRs show coexisting pulmonary disease, often not.

Diagnosis depends on the involved organ.  For renal TB (e.g. persistent culture-negative pyuria), order urines for AFB.  Most other sites require FNA or biopsy with culture.  Biopsy smears have very low yields for actual bacilli, so you may have to wait for culture results.  But if “caseating granulomas” (“cheesy”) are noted on a path report, it’s TB.  All other granulomas (sarcoid, etc.) are “non-caseating” [try telling a patient they have a “cheesy granuloma”].

Extrapulmonary TB is not contagious.  Nor is TB of the pleura.  Only parenchymal Pulmonary TB (& the rare Laryngeal TB) can be transmitted.  Smear-positive Pulmonary TB is infectious.  Smear-negative much less so; only ~25% of ongoing household contacts become infected.  Compare that to measles, pertussis, or influenza, which can transmit in waiting rooms.

PPD ?????   As noted in prior postings, a PPD plays minimal role in the work-up of active TB.  It’s good to place one, but 20% of Active TB patients may test negative.  Many will convert to positive once treatment improves immune function.  There’s less data on the IGRA.

And if it’s positive, just means they have Latent TB (have had it since whenever), with current symptoms not at all necessarily related.  Indeed, patients with a positive PPD and abnormal chest x-ray may be more likely to have imminently-fatal pneumococcal pneumonia than insidious Active TB.  However, an abnormal CXR with positive PPD/IGRA makes Public Health referral a lot easier.

Moral  —  NEVER claim to “R/O Active TB” by noting “negative PPD.”

SUMMARY OF ACTIVE TUBERCULOSIS

• Cough > 3 weeks duration (if not starting to improve, & no alternative Dx) warrants CXR
• CXR sooner for hemoptysis, fever, weight loss, night sweats
• PPD / IGRA OK but not useful (20% false-neg; Pos. is non-specific)

• 3 Sputum specimens (different days) for AFB
• Order PCR on 1^st specimen if high index of suspicion
• Begin 4-drug Tx (by DOT) if high index of suspicion
• Isolation if high index of suspicion (confine to home)
• If high index of suspicion: all Dx & Tx should be managed by Dept. Public Health TB Control

• AFB smears ready in 24 hrs.
• Smear-Positive = presumptive TB → Tx!
• Smear-Negative may get empiric Tx pending cultures (judgment call)
• Cultures take 1-2 weeks by radiometric technology
• If negative, must wait full 60 days for no-growth on conventional media to say “Negative”
• If pos., Susceptibility Results take another 1-2 wks.

• Presents with weight loss, night sweats, &/or fevers
• Specific Sx depend on involved organ
• Dx by FNA / Biopsy (“urine for AFB” for renal TB; CSF for TB meningitis)
• “Caseating Granulomas” on histology = TB
• Smear for AFB gives poor yield; must await Cultures (long wait)

And that’s it for TB (previously known as “Consumption”).