Pneumocystis jirovecii pneumonia in autoimmune rheumatic diseases: a nationwide population-based study

Abstract

Objective To compare Pneumocystis jirovecii pneumonia (PJP) risk between patients with autoimmune rheumatic diseases (ARD) and the general population Methods We identified patients with ARD recorded in the National Health Insurance Research Database of Taiwan from 2002 to 2015 and randomly selected a comparison cohort from the general population matched for age and sex. We analyzed PJP risk stratified by sex, age, comorbidities, and medications using Cox proportional hazard model. Results We enrolled 103,117 patients with ARD. PJP risk significantly increased in patients with any ARD and with each individual ARD like rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), Sjogren’s syndrome (SjS), polymyositis and dermatomyositis (PM/DM), systemic sclerosis (SSc), and systemic vasculitis. Patients with PM/DM showed prominent risk with incidence rate of 12.47/100,000 patient year (95% confidence interval (CI), 32.16–86.70). In a time-dependent Cox proportional hazard model with comorbidities and medications as covariates, PM/DM, SSc, SLE, and SjS significantly increased adjusted hazard ratios (aHR) of 5.40, 5.12, 4.09, and 3.64, respectively (95% CI of 2.82–10.35, 2.16–12.13, 2.41–6.95, and 2.06–6.42, respectively). AHR after adjusting for male sex, cancer, human immunodeficiency virus infection (HIV), and interstitial lung disease also significantly increased. Use of daily oral steroid dose of >10 mg conferred the highest risk followed by mycophenolate. Use of injected steroids, cyclophosphamide, biological agents, methotrexate, and cyclosporine conferred a significantly higher risk. Conclusion Underlying ARD significantly predisposes patients to PJP, with PM/DM posing the highest threat. In addition to underlying disease, comorbidities and concomitant immunosuppressants are major risks. The strongest risk is recent daily steroid dose of >10 mg. Mycophenolate seems to be a more prominent risk factor than cyclophosphamide. Key Points • Autoimmune rheumatic diseases (ARD) significantly increased the overall risk of PJP, and so did each individual ARD. • Use of steroids, mycophenolate, cyclophosphamide, biological agents, methotrexate, and cyclosporine all significantly increased risk of PJP. • Male, elderly, malignancy, HIV, and interstitial lung disease are also related to increased risk of PJP. • Underlying ARD, comorbidities, and use of immunosuppressant should all be considered in determining the overall risk of PJP.

Application value of blood metagenomic next-generation sequencing in patients with connective tissue diseases

“…The incidence of P. jirovecii in CTD is uncommon and quite difficult to diagnose. However, autoimmune rheumatic diseases significantly increased the overall risk of P. jirovecii infection compared to healthy individuals, especially SLE and DM/PM ( 19 , 20 ); it portends high mortality, yet is a largely preventable complication of rheumatic disease treatment ( 21 , 22 ). Still, it remains a grave concern in CTD patients due to its high mortality rate ( 22 – 24 ).…”

Acute Pneumocystis jirovecii Pneumonia Due to Absolute Lymphopenia

“…Corticosteroids alone do not increase the PCP risk as a similar effect is not seen in all AIIDs, indicative of AIIDs being an independent risk factor [2]. Corticosteroid risk depends on the total dose, duration, and daily doses [5]. A daily corticosteroid dose of ≥20 mg prednisone equivalent for ≥4 weeks is considered a PCP risk factor [11].…”

“…A daily corticosteroid dose of ≥20 mg prednisone equivalent for ≥4 weeks is considered a PCP risk factor [11]. Compared to other immunosuppressants, a daily dose of ≥10 mg prednisolone equivalent had the highest risk for PCP, while MTX risk was low [5]. In patients with RA treated with a daily corticosteroid dose of <10 mg prednisolone equivalent, concurrent MTX was a substantial causative factor for PCP occurrence [3,10].…”

“…An infrequent severe, life-threatening side effect of MTX is an increased risk of PCP. In non-HIV patients, the mortality rate of PCP is high (39.4%-59.1%) [5]. Here, we present an elderly Caucasian female with RA on immunomodulatory therapy manifesting with acute respiratory failure requiring mechanical ventilation due to PCP.…”

Exploring the Differences in Pneumocystis Pneumonia Infection Between HIV and Non-HIV Patients

“…An additional subset of patients who are at high risk of PCP infection in patients with inflammatory and autoimmune disorders include patients with polymyositis, Wegener's granulomatosis, dermatomyositis, polyarteritis nodosa, and rheumatoid arthritis. The risk in this group is much higher with the coadministration of immunosuppressant drugs such as methotrexate, antitumor necrosis factor (TNF) alpha, and anti-interleukin (IL)-6 receptor antibody, considering the risk is also higher for male patients and patients above 60 years old [16]. Children and adolescents are also at risk of developing PCP infection, especially those patients with gene mutations that affect T-cell function, most commonly in patients with severe combined immunodeficiency and adenosine aminase mutation disorders.…”