Steroids, Prophylaxis and Pneumocystis Pneumonia Save

A case-control study has shown that glucocorticoids and tapering glucocorticoids are risk factors for the development of Pneumocystis jirovecii pneumonia (PJP). The authors provide guidance on the optimal timing for prophylaxis use and withdrawal. 

This case-control study included 1,294 prophylactic episodes in 1,148 patients with rheumatic disease who received immunosuppressants and prophylactic trimethoprim-sulfamethoxazole (TMP-SMX). The most common underlying diagnosis was SLE (n=273, 21.1%), followed by ANCA-associated vasculitis (AAV) (n=226, 17.5%) and idiopathic inflammatorymyositis (IIM) (n=204, 15.8%). The most commonly used immunosuppressant was cyclophosphamide (20%), rituximab (13%), mycophenolatemofetil (9%), azathioprine (9%), tacrolimus (5%), and cyclosporineA (5%).  

The primary outcome was a one-year incidence of PJP.

They identified 10 PJP cases (from 1,174 person-years followup) with an incidence rate of 0.85 per 100 person-years. These patients were on TMP-SMX prophylaxis for a mean of 182 days.  In 9/10 case, PJP occurred after discontinuation of TMP-SMX, after a median of 117 days. Those developing PJP tended to be older, with lymphopenia and compromised renal function, and had a shorter duration of TMP-SMX (median 148 vs. 51 days). 

In multivariate analysis, risk factors for PJP included age, impaired renal function, lymphopenia, rituximab use and higher doses of GC at the time of TMP-SMX discontinuation. 

Key factor in PJP infection:

• The dose of glucocorticoids at the time of TMP-SMX discontinuation was significantly higher in the PJP group relative to the control group (22 vs 10 mg). 
• Discontinuing TMP-SMX while on a glucocorticoid dose >12.5 mg/day significantly increased the risk of PJP (adjusted hazard ratio: 13.84). 

Tapering glucocorticoids to 12.5 mg/day (prednisone equivalent) could be a reasonable timepoint to initiate the withdrawal of PJP prophylaxis in patients with rheumatic diseases.