Sarcoidosis is often treated with high-dose oral corticosteroids for extended periods of time. Anytime we prescribe oral corticosteroids, my fellow always wants to start trimethoprim-sulfamethoxazole (TMP-SMX) prophylaxis against Pneumocystis jirovecii pneumonia (PJP). This seems to have become dogma when treating sarcoidosis, but I'm not sure it's justified.
About a decade ago, I did a "deep dive" on the topic of PJP prophylaxis for patients with sarcoidosis who were taking corticosteroids. I had never seen a patient with sarcoidosis who developed PJP, and one of the older and more experienced attendings at my clinic said she hadn't either, despite the fact that we'd both used prolonged courses of corticosteroids to treat patients with sarcoidosis. I had my fellows review recent records from our clinic, and we found eight patients who had received more than 30 mg of prednisone equivalent per day for more than 30 days and had not received PJP prophylaxis. None were diagnosed with PJP.
Okay, eight is a small sample size. But we also did an informal literature search on the topic of PJP, sarcoid, and oral corticosteroids. We didn't find much — a case series from France that reported five patients with sarcoidosis and opportunistic infections, one due to PJP; four individual case reports; and one larger review on PJP prevalence in the presence of oral corticosteroids that included one patient with sarcoid. Two of the six total patients we found were lymphopenic at the time of diagnosis, with CD4+ T-cell counts below 200 cells/µL. Two others had been taking steroids for 3-4 months prior to diagnosis.
So, six patients in the history of sarcoid had PJP, as of 2011 or so. This, on a background prevalence of 4.6-64 per 100,000 individuals. If that's too much math, let's just say there are plenty of patients walking around with sarcoid and many will be treated with oral corticosteroids, yet PJP cases are as infrequent as a postseason Orioles game. Do we really need to subject our patients with sarcoidosis to TMP-SMX?
Our literature search turned up a few other papers of interest. An observational study published in 1996 in Mayo Clinic Proceedings reported on over 100 patients without HIV who had been diagnosed with PJP. One quarter had been diagnosed with PJP after receiving corticosteroid doses as low as 16 mg/d for as few as 8 weeks. Underlying disease processes and indications for oral corticosteroids were heterogeneous; only one of the patients had sarcoidosis. Unfortunately, the occurrence of PJP was part of their patient selection criteria, so we don't know the denominator (how many total patients received corticosteroids over the time period and weren't infected) and can't calculate a PJP prevalence. Given that the patients were taken from a specialty, tertiary referral center over a period of 6 years, one would expect the denominator to be high.
Another paper from Mayo Clinic Proceedings, this one a meta-analysis, was more helpful. It reported numbers needed to treat (NNT) and harm (NNH) when using TMP-SMX to prevent PJP. The investigators broke these numbers down by underlying condition and found the NNT to prevent PJP in patients with connective tissue disease is anywhere from 110 to 1099. PJP rates with sarcoid weren't specified, presumably because there's so little data available. However, extrapolating from connective tissue disease rates, one would assume the NNT for sarcoid fell in the same range and far exceeded the NNH with TMP-SMX of 32. One caveat: It wasn't clear how the presence of exogenous immunosuppressive agents was factored into these estimates.
Despite the limits in these data, I began telling my fellows not to use TMP-SMX prophylaxis when starting a patient with sarcoidosis on oral corticosteroids. Ever the academic contrarian, I relished the chance to buck the conventional wisdom. I dazzled them with NNTs and NNHs they weren't familiar with (the concept or its application to the question at hand). Some withheld TMP-SMX; others just found a different attending to talk to. But I felt smart.
On closer inspection though, I was overconfident. While assessing the risk-benefit of routine prophylaxis may seem a quotidian task, it's a critical exercise. Nonetheless, a precise risk-benefit assessment isn't possible with the data we have. We're left with extrapolations. On the one hand, the underlying condition factors into the likelihood that a patient on corticosteroids will develop PJP. Both anecdotal experience and the literature imply that it rarely occurs with sarcoid. On the other hand, PJP prophylaxis works, non-HIV PJP has a 20%-40% mortality (maybe higher), and side effects from TMP-SMX are usually mild and reversible. Furthermore, the presence of underlying pulmonary disease increases PJP mortality. So perhaps the underlying lung function of your patients with sarcoid should factor into the decision about providing prophylaxis.
What to do? Double down and act confident? Display some humility? Since I'm not a surgeon, I'll opt for the latter. It hurts me to say, but one of the more intelligent editorials I read on this topic was written by two rheumatologists. I assume they had to stay in the hospital past four in the afternoon to research and complete their paper. Who knew rheumatologists even did that? Joking aside, although they were talking about connective tissue disease, they outlined an individualized approach that could be applied to sarcoid. If the patient is receiving cyclophosphamide or has a history of PJP, they give prophylaxis. If not, they order lymphocyte counts and withhold prophylaxis in the absence of lymphopenia or a CD4+ count below 200 cells/µL.
For most patients with sarcoidosis, I'm using 20-40 mg per day of prednisone equivalent and tapering down after approximately 4 weeks. So, unless there are lymphocyte abnormalities, I won't be reflexively starting TMP-SMX. If my patient is on alternative immunosuppressive agents that confer higher risk or have a better established risk-benefit profile for prophylaxis, I'll adjust accordingly. I'll be pursuing this approach with considerably less confidence than I had when I began writing this.
Aaron B. Holley, MD, is an associate professor of medicine at Uniformed Services University and program director of pulmonary and critical care medicine at Walter Reed National Military Medical Center. He covers a wide range of topics in pulmonary, critical care, and sleep medicine.
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Cite this: Aaron B. Holley. Do We Really Need to Subject Our Patients With Sarcoidosis to TMP-SMX to Prevent PJP? - Medscape - May 24, 2022.