Thread by @WuidQ

#idgrandrounds
Presented by @LParraRod
1/2
Man in his 60's, on-going temozolamide + dexa for glioblastoma, p/w 1 wk b/l knee arthritis, preceded by 4 d fever & watery diarrhea.

H/o DLBCL in remission x 4 yrs, mild b/l knee OA
Recently stopped TMP-SMX for unclear reason.

2/2
Immigrated to the US from El Salvador 20 yrs ago. No recent travel, pets, illicits. Lives in IL.

WBC 3.6. CMP u/r
Synovial fluid: WBC 85K (80%N)

Approach, DDx? @TxID_Edu @CarlosSaldana @k_vaishnani @VarunPhadke2 @UAB_ID @BIDMC_IDFellows @IUIDfellowship @LeMiguelChavez

1/12
CASE RESOLUTION:
Blood & synovial fluid culture +Salmonella typhimurium

Great job! All of you got the right answer and included the most important differential diagnoses.

Takeaway points from this case: approach to arthritis & diarrhea, implications of temazolamide Tx

2/12
Approach to arthritis & diarrhea

Is diarrhea a noise or a signal. It usually takes a “leap of faith” to answer this question. Let’s take that leap and say that the diarrhea here is a signal.

Important cosiderations in formulating DDX: tempo of illness & the host

3/12
Diarrhea ➡️ arthritis
▪️Diarrhea preceding the onset of arthritis by several days to several weeks (usually 1-4 weeks) 👉 reactive arthritis from enteric pathogens (Salmonella, Shigella, Campylobacter, Yersinia)

4/12
Diarrhea + arthritis (chronic)
▪️Diarrhea + arthritis (+ wt loss) 👉 triad seen in 75% of Whipple dx at presentation. Diarrhea follows years of migratory arthritis (arthritis ➡️ diarrhea)
▪️IBD, bowel-associated-dermatosis-arthritis syndrome (yes, it’s called BADAS sx) 😊

5/12
Diarrhea + arthritis (acute)
▪️Acute diarrhea occurring with (or preceded by a few days) arthritis 👉 disseminated infection (septic bacterial arthritis)
▪️The acuity of symptoms speaks of enteric bacterial pathogen as cause

6/12
It’s always important to calibrate you DDX with the characteristics of the host:
▪️Immune status
▪️Exposure history (a guide is presented 👇; by no means complete but can be helpful)

https://twitter.com/WuidQ/status/1202612608785764353

7/12
We can re-state our problem representation as:

▪️An immunocompromised patient (let us assume for now that temozolamide is an immunocompromising agent), who p/w acute inflammatory arthritis and diarrhea

8/12
The fact that the diarrhea occurred a couple of days before the arthritis makes reactive arthritis less likely.

The acute presentation makes mycobacterial (esp. TB), fungal (esp. endemic fungi), atypical bacterial (e.g. Whipple disease), or protozoal less likely.

9/12
This leaves us with enteric bacterial infection. Disseminated infection involving the joint has been reported for E. coli, Campylobacter, Yersinia, Shigella, and Salmonella.

But among them, the latter is probably the most notorious for causing osteoarticular infection.

10/12
Risk factors of Salmonella osteoarticular infection: sickle disease, immunosuppression (e.g. HIV, immunosuppressive drugs, CGD).

11/12
Temozolamide is an alkylating agent that causes isolated CD4 lymphopenia as @k_vaishnani pointed. It develops in 60% of patients and can last up to 245 days after stopping the drug.

ascopubs.org/doi/10.1200/JC…

12/12
Apart from disseminated salmonellosis pubmed.ncbi.nlm.nih.gov/18715650/ other OIs have also occurred with temozolamide.

PCP prophylaxis, recommended for while on temozolamide/steroids. In this patient, stopping TMP-SMX further ⬆️ risk of disseminated salmonellosis.