Risk factors of Pneumocystis jeroveci pneumonia in patients with systemic lupus erythematosus
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- Lertnawapan, R., Totemchokchyakarn, K., Nantiruj, K. et al. Rheumatol Int (2009) 29: 491. doi:10.1007/s00296-008-0721-6
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Pneumocystis jeroveci pneumonia (PCP) is an opportunistic infection which occurs mostly in the immune-deficiency host. Although PCP infected systemic lupus erythematosus (SLE) patient carries poor outcome, no standard guideline for prevention has been established. The aim of our study is to identify the risk factors which will indicate the PCP prophylaxis in SLE. This is a case control study. A search of Ramathibodi hospital’s medical records between January 1994 and March 2004, demonstrates 15 cases of SLE with PCP infection. Clinical and laboratory data of these patients were compared to those of 60 matched patients suffering from SLE but no PCP infection. Compared to SLE without PCP, those with PCP infection have significantly higher activity index by MEX-SLEDAI (13.6 ± 5.83 vs. 6.73 ± 3.22) or more renal involvement (86 vs. 11.6%, P < 0.01), higher mean cumulative dose of steroid (49 ± 29 vs. 20 ± 8 mg/d, P < 0.01), but lower lymphocyte count (520 ± 226 vs. 1420 ± 382 cells/mm3, P < 0.01). Interestingly, in all cases, a marked reduction in lymphocyte count (710 ± 377 cells/mm3) is observed before the onset of PCP infection. The estimated CD4+ count is also found to be lower in the PCP group (156 ± 5 vs. 276 ± 8 cells/mm3). Our study revealed that PCP infected SLE patients had higher disease activity, higher dose of prednisolone treatment, more likelihood of renal involvement, and lower lymphocyte count as well as lower CD4+ count than those with no PCP infection. These data should be helpful in selecting SLE patients who need PCP prophylaxis.
Pneumocystis jeroveci pneumonia (PCP), previously known as Pneumocystis carinii  is an opportunistic infection which occurs almost exclusively in the immunocompromised host with and without acquired immune deficiency syndrome (AIDS) [2, 3]. The incidence of PCP was increase during the AIDS era with a marked decline in mid 1992 probably due to the introduction of PCP prophylaxis . On the contrary, PCP in non-AIDS connective tissue disease patients was increased [5–17] and showed higher mortality rate than PCP in AIDS patients [2, 5]. Systemic lupus erythematosus (SLE) with PCP was also observed to be acute at onset, severe and most of all with high mortality . Previous studies [2, 14, 18, 19] indicated the risk factors for PCP infection in SLE as lymphopenia, increased LDH, interstitial fibrosis, high dose of corticosteroid and cytotoxic drugs. The aim of our study is to further identify the risk factors of PCP infection in Thai patients with SLE which may add on useful information for establishment of guideline for PCP prophylaxis in SLE.
Patients and methods
Source of data
Patients were identified through a search of Ramathibodi hospital medical records between January 1994 and March 2004.
Fifteen cases of SLE with PCP were identified by ICD-10. The diagnosis of SLE fulfilled the 1982 American College of Rheumatology revised classification criteria for SLE, while the diagnosis of PCP was made by (1) a compatible clinical presentation including dyspnea, fever, cough, and in most cases a newly recognized infiltrate on the chest roentgenogram; (2) an associated underlying condition compromising immunologic function; and (3) sputum or branchoalveolar lavage organisms that was dectected by using Grocott Methenamine Silver stain or immunofluorescence antibody staining (IFA) .
The 60 patients without PCP in the control group were selected by the table of randomization from the consecutive age and sex matched SLE patients who were monitored regularly over the same period at Ramathibodi hospital. The usual clinical and biological data at diagnosis and during the follow-up period were collected. PCP infection usually occurs within 6–7 months after initiation of SLE immunosuppression therapy. The control group is also selected from the same period (after treatment) for comparison. The doses and mode of administration of corticosteroid and cytotoxic drugs were recorded. Any subject with the human immunodeficiency virus (HIV) was excluded from the study.
Data from patients and controls were compared using the Chi-square test for categorical variables, and the Mann–Whitney U test for quantitative variables. The hypothesis was examined based on two-tailed P values. The test values of 0.01 or less were considered as statistically significant. We also used the Odd ratio to determine the significant of the risk factor for PCP.
Demographic and biological data of SLE patients with and without PCP
Number of case
Age (mean ± SD)
37 ± 10
37.1 ± 14.3
13.6 ± 5.83
6.73 ± 3.22
Autoimmune hemolytic anemia
Central nervous system involvement
Interstitial pulmonary fibrosis
Prednisolone (mean ± SD)
49 ± 29
20 ± 8
Cyclophosphamide (mean ± SD)
78 ± 33
74 ± 18
Azathioprine (mean ± SD)
62 ± 50
54 ± 20
Chloroquine (mean ± SD)
230 ± 8
238 ± 10
White blood cell counts (mean ± SD)
6,462 ± 1943
7,700 ± 2100
Polymorphoneuclear cell counts (mean ± SD)
4,995 ± 1642
5,870 ± 780
Lymphocyte counts (mean ± SD)
1,040 ± 438
1,842 ± 632
Minimal lymphocyte counts (mean ± SD)
520 ± 226
1,420 ± 382
Lymphocyte counts when PCP occurs
710 ± 377
Delta lymphocyte (mean lymphocyte counts − lymphocyte counts at onset PCP)
329 + 210
156 ± 5
276 ± 8
Although we did not measure CD4 count, the estimated CD4 count, which can be calculated from 15–20% of lymphocytes, was lower in PCP infected patients than in the controls (156 ± 5 vs. 276 ± 8; Odd ratio 6.71, 95% CI 4.42–9.46).
From our study, the mortality rate of SLE patients infected by PCP is 20%. This high mortality rate signifies the importance of PCP prophylaxis in high risk SLE patients as has been done in AIDS patients .
Comparison of risk factors and suggestions for PCP prophylaxis between various studies
Godeau et al. 
Li et al. 
Kadoya et al. 
Galeazzi et al. 
Porge et al. 
Lertnawapan et al.
Connective tissue disease
Mean/median lymphocyte count in PCP versus control (cells/mm3)
preRx. 1,060 vs. 1,426
352 ± 152 in PCP
1052.7 ± 309.1 vs. 1841.6 ± 632.4
595 vs. 833
1,040 ± 438 vs. 1,842 ± 632
Lowest lymphocyte count in PCP versus control (cells/mm3)
244 versus 738
959.3 ± 196 vs. 1663.9 ± 682.4
520 ± 226 vs. 1420 ± 382
Lymphocyte at onset PCP (cells/mm3)
710 ± 377
87 ± 78
156 ± 5
Prednisolone or immunosuppressive treatment
Cyclophosphamide 1.67 versus 0.97 mg/kg per day
Prednisolone 25–60 mg/day and Immunosuppressive
No significant of dose of Prednisolone
Prednilosone 43 vs. 20 mg/day
Prednisolone 49 ± 29 vs. 20 ± 8 mg/day
CD4 < 250
High dose immunosuppressive
Lymphocyte < 600
CD4 < 250
Risk of PCP
Interstitial Pulmonary Fibrosis
Lymphocyte < 350
High steroid dose
Lymphocyte < 750
Prednisolone > 20 mg/day
CD4 < 150
Renal involvement or hight disease activity
Other significant risk factors for developing PCP demonstrated by our study were high disease activity, renal involvement and high prednisolone dosage. The result that MEX-SLEDAI was higher in the PCP group than in control confirmed the effect of the severity of disease on the occurrence of PCP.
Contrary to the study by Kadoya et al.  which demonstrated interstitial pulmonary fibrosis as a significant risk factor, our study showed that only the renal involvement correlated significantly with the higher incidence of PCP infection.
All our 15 PCP infected SLE patients had been treated with prednisolone at the mean dosage of 49 ± 29 mg/day which was significantly higher than the mean dose in the control group. This is in contrast with previous study by Kadoya et al. , which showed no significant correlation between the steroid dosage and the risk of PCP infection. Nevertheless, our finding is in agreement with the recommendation to start the PCP prophylaxis in patients who received more than 20 mg prednisolone equivalent per day .
Unlike previous study by Godeau et al. , we could not find any significant correlation between PCP infection and the use of other immunosuppressive agents such as cyclophosphamide and azathioprine (Table 2).
Although this study is limited by the small number of PCP infected SLE patients and insufficient laboratory data for analysis, a demonstration of a profound decrease in lymphocyte count prior to the onset of PCP infection should be clear enough to be included in the standard guideline for PCP prophylaxis in SLE.