Most previous studies of HIV-negative patients with PCP focused on hematological malignancies, CTD and organ transplantation. To the best of our knowledge, this is the first study about PCP in patients with PNS. Among 5400 PNS patients seen in our hospital in the past 13 years, we found 18 patients with PCP˗ an incidence was 0.3%. Because of the low specificity of the polymerase chain reaction (PCR) for the detection of P. jirovecii DNA [13, 14], we excluded suspected cases with positive PCR but negative staining. Thus, the actual incidence of PCP would be higher than 0.3%. This prevalence of PCP was lower than that in patients with non-Hodgkin’s lymphoma and kidney transplant, which were 0.94% and 0.91%, respectively in one study 15, but similar to that in patients with rheumatoid arthritis (0.2–0.4%) [16, 17].
In this study, we found that PNS patients with PCP were receiving a higher prednisone dose (average 31.3 mg/d) at the time of hospitalization, and 13 patients (72.2%) developed PCP around 3 to 6 months after the initiation of prednisone therapy. These findings indicated that PCP was more likely to appear 3 to 6 months after the initiation of immunosuppressive therapy, when patients did not achieve a complete remission, and were still receiving large doses of prednisone. Findings were similar in two previous studies of PCP in HIV-negative patients [18, 19]. Also, like HIV-uninfected individuals, patients with PCP in our study typically had a rapid onset, fast progression to respiratory failure, shorter symptoms duration, higher risk of co-infections and were more likely to require ICU admission compared to HIV-infected patients [20, 21].
Although not fully characterized, the known risk factors for PCP in HIV-infected patients include underlying diseases (hematologic malignancies and CTD), use of glucocorticoids, chemotherapeutic agents, immunosuppressive agents, or monoclonal antibodies, low CD4 + cell counts and lymphopenia [22–24]. In our study, we also found that a lower CD4 + cell count was an independent risk factor for PCP. With the exception of patients with HIV, the CD4 + cell count was also a main risk factor for PCP or opportunistic infections in kidney transplant recipients and those with CTD [25, 26]. Glucocorticoids could cause rapid redistribution of lymphocytes from the circulation, depleting circulating CD4 + T cells, and to a lesser extent CD8 + T cells [27]. Different studies have demonstrated that steroid therapy increased the susceptibility to infection because of impairment of cellular immunity [28, 29].
The most important finding in our study was that all PNS patients with PCP survived and no patients died, which indicated a better outcome in these patients than in those with other conditions. Previous studies have found a higher mortality of 2 to 28% in patients with rheumatoid arthritis [30], 13 to 43% in patient with kidney transplant [31], and 30 to 60% in patients with hematological malignancies [23]. According to previous studies, possible prognostic factors in HIV-negative patients were old age, co-infections, respiratory failure, pre-existing lung disease and a higher LDH level [32–34]. The reason that no patients died in our study may be due their relatively younger age (average 48.5 years) and the disease itself. Torres et al. did a study of immunosuppressive treatment in 19 patients with membranous nephropathy and found 2 patients with PCP, both of whom survived [35]. Other investigators have also reported survival in cases of PCP infection in patients with PNS [36, 37]. In a 10-year retrospective study of 60 non-HIV Chinese children diagnosed with PCP, 2 of 8 (25%) with PNS died, while 23 of 52 (44.2%) with CTD died [38]. Wan et al. reported four patients with severe PCP and immunoglobulin A nephropathy, one of whom died [39]. These studies all indicated that PNS patients with PCP may have a better outcome than patients with other underlying conditions.
In conclusion, this study demonstrated that compared to HIV-negative patients, PNS patients had a higher incidence (0.3%) of PCP, and also had the same clinical characteristics as those with PCP. The most important risk factor was a lower CD4 + count caused by steroid or immunosuppressive therapy. However, PNS patients had a better outcome than other patients with PCP.