There are some widely used prognostic guidelines for CAP. These systems appear to be useful in assisting physicians to make more rational decisions regarding the need for admission [13–15]. Patient mortalities in the risk groups 3–5 on A-DROP and CURB-65, and IV-V on PSI have previously been reported as 11.5–23.3%, 11.6–21.0% and 12.5–29.2%, respectively [16–19]. A striking fact is that the majority of the PCP patients were categorized as mild to moderate by these guidelines and resulted in respiratory failure, and poor outcomes. We emphasize that mortality prediction in PCP is not correct when these conventional guidelines for CAP are applied, even when PCP develops in the setting of CAP. Also, these guidelines definitely underestimate the severity of PCP as CAP. The important issue is why these guidelines cannot correctly estimate PCP severity. PCP without HIV infection shows quite different clinical pictures compared to PCP with HIV infection. PCP with HIV occurs slowly and gradually . On the other hand, PCP without HIV is typically more acute and severe than when associated with AIDS , often resulting in acute respiratory failure requiring a need for mechanical ventilation. We suppose that this results from the differences of pathologic mechanisms between PCP with and without HIV. It is evident that PCP without HIV is an allergic reaction originating from Pneumocystis jirovecii. Pneumocystis elicits many kinds of immune responses, including those by lymphocytes, macrophages, neutrophils, dendritic cells, and epithelial cells [1, 21]. There is now a considerable body of evidence showing that immune and inflammatory responses to Pneumocystis can have harmful as well as beneficial effects on host lungs.
Another reason why the mortality rate of PCP without HIV remains high is presumably that it is difficult to diagnose PCP according to nonspecific signs, symptoms and/or no reliable culture. Bollée et al. documented that the leading symptoms of PCP in HIV-uninfected cancer patients were fever (85.7%), dyspnea (78.6%), cough (57.1%), and all three symptoms (44.6%) on diagnosis , and 14.3% of the patients showed only one symptom. In our study, 4 out of 21 patients (19%) were asymptomatic. In addition, 6/21 patients (28.6%) showed abnormality in chest X-ray on admission. It is possible that steroids and immunosuppressive drugs could mask fever and general fatigue on the initial visit. We strongly believe that clinicians are unable to diagnose non-HIV PCP by clinical picture or chest X-ray alone. The association with P. jirovecii cysts has been reported in HIV-uninfected PCP to be one tenth of that in HIV-PCP . Therefore, the sensitivity of conventional staining methods for diagnosis of HIV-uninfected PCP is lower than that for PCP with HIV. Our study demonstrated the sensitivity of conventional staining to be 23.8%. While Diff-Quik staining is highly sensitive, it requires considerable technical expertise . It is likely that physicians are unable to diagnose PCP without HIV soon enough due to the reasons mentioned above.
A clue for making the early diagnosis of PCP is serum β-d-gulcan (β-DG) and chest CT findings. Tasaka et al. reported the β-DG could be a serum indicator for the diagnosis of PCP with the cut-off value of 31 pg/ml [23, 24]. In our study, the sensitivity of β-DG in diagnosing PCP was 10/21 (47.6%) setting the cut-off value at 31 pg/ml. We suggest that testing β-DG is effective for diagnosis of PCP. In testing, BAL is also well known to be more sensitive than IS, as many physicians previously reported [23, 25]. In terms of a radiological approach, high resolution computed tomography (HRCT) should be performed if PCP is suspected. It is commonly known that chest CT shows ground glass appearance with a panlobular pattern or so-called crazy paving appearance in PCP patients [26, 27]. These findings are also found in viral pneumonias, mycoplasmal pneumonia, alveolar hemorrhage, methotrexate pneumonia, and others. However, where the patient’s background and characteristics are conducive, the presence of PCP should be suspected.
Conventional guidelines for CAP have recommended that clinical outcomes should be evaluated three days after initial therapy has been started [13, 28–33]. In our study, 12 of the 13 (92.3%) patients who received accurate anti-PCP therapy within 3 days from initial visit were cured. Ten of the 12 (83.3%) patients received empiric therapy for PCP based on patient characteristics, laboratory data and radiological findings on HRCT. On the other hand, 7 of the 8 (87.5%) patients who received anti-PCP therapy that was initiated after day 4 died. PCP without HIV tends to develop acute respiratory failure and results in a more severe, acute form of acute respiratory distress syndrome (ARDS) than PCP with HIV. Thus, only three days of doctor’s delay in starting PCP therapy could be fatal as our study showed.
The limitation of our study is that it is a retrospective analysis in a very small population. Retrospective studies may be less reliable in terms of the data collected, particularly for data such as physical examination. A prospective study should be carried out and with more cases.