Thread by @FilaMentor

A one tweet question! #GalactoMagic

60M w/ asthma from China presents w/ SOB secondary to an asthma exacerbation. He has never smoked cigarettes. A CT chest shows a 7mm right upper lobe nodule

Which of the following tests should be ordered for further evaluation of the nodule?

1/14
Answer: AFB sputum culture

Without knowing much about the patient, other than age, geographic risk, smoking status, & normal immune status, most common infectious cause of a solitary pulmonary nodule (SPN) is TB.

2/
It’s possible that the SPN may be latent TB, but we need to rule out active TB first (AFB sputum cultures x3) before considering latent TB

Fungal causes are less likely. If we want to work it up, it would be pathogen specific (e.g., Cocci Ab) & not broad antigen testing (BDG)

3/
A SPN is defined as opacity <3cm surrounded by lung tissue. The ⬆️use of CT scans has led to ⬆️ detection of nodules. Clues to suggest a malignant process include
🍏size >1cm
🍎doubling time 1mo-1y
🍐spiculated
🍊asymm calcification
🍋nonsolid

pubmed.ncbi.nlm.nih.gov/26760594/

4/
SPNs can be either benign or malignant

Probability of malignancy is based on:
🌞nodule characteristics
🌞patient risk factors
🌞prediction models

Management includes serial imaging vs sampling

5/
The prevalence of each etiology varies among different populations, with the approach depending on patient epidemiologic risk (geography, immune status)

People from Asia and South America are more likely to have infectious causes of SPN vs those in Europe and North America

6/
The differential diagnosis for SPN is broad. It’s broken down into malignant and benign causes

Of the benign causes, infectious etiologies have been reported to account for 15% of cases in American studies

pubmed.ncbi.nlm.nih.gov/24624288/

7/
Once you have this framework, you can layer on the incidence of these etiologies based upon:
🌙where the patient is from
🌙risk factors for cancer vs infection
🌙immune status

In this patient from China with no prior smoking history, the nodule is TB until proven otherwise

8/
Fungal infections cause SPN, but generally seen in immunocompromised patients (w/ Aspergillus & Crypto)

Endemic fungi (e.g., Histo) can cause SPN in immunocompetent hosts, but the work up is focused on specific pathogen (e.g., Histo Ab), and not on broad antigen testing (BDG)

9/
For example, Histo SPN represent healed infection w/ no live organisms. Thus, antigen testing is usually negative

Cultures of SPN are rarely positive as the organisms are nonviable

The test of choice is Histo antibody (represents prior infection)

pubmed.ncbi.nlm.nih.gov/32000281/

10/
There is no guidance/algorithm on when to think about fungal infections for SPN

As we mentioned, it’ll depend on nodule characteristics, geographic risk, immune status, & RF for fungal infections

This table of RF for fungal infections can guide our fungal work up for SPN

11/
So, you see a SPN that’s likely infectious

You review the geographic risk & RF in the table above

Depending on the fungus, you can send the following serologic tests:

- Crypto➡️Crypto Ag
- Aspergillus➡️GM
- Histo➡️Histo Ab
- Cocci➡️Cocci Ab
- Blasto➡️Blasto Ab

12/
PJP can cause SPN, but it is usually multiple. More importantly, it is very rare for PJP to only cause nodules

Mucorales order can cause multiple nodules, but BDG and GM are not helpful as they will be negative (cell wall doesn't have BDG or GM)

Candida does not cause SPN

13/
This is in contrast to MULTIPLE pulmonary nodules (MPN), where the differential diagnosis lies not only on patient RFs, but also in nodule distribution

Infectious causes are in the lympho-hematogenous or primary bronchiolar distribution categories

pubmed.ncbi.nlm.nih.gov/16537886/

14/
In sum, the evaluation for SPN differs based on incidence of etiologies of a SPN for a patient, focused on geography, RF (smoking), immune status (HIV), & nodule characteristic (size)

Work-up for fungal infections include specific pathogen testing in immunocompetent hosts