High prevalence and mortality of Pneumocystis jirovecii pneumonia in anti-MDA5 antibody-positive dermatomyositis.

To identify potential risk factors and prognostic factors of Pneumocystis jirovecii pneumonia (PJP) infection in anti-melanoma differentiation-associated gene 5 antibody-positive DM (anti-MDA5+ DM) patients, and to evaluate the diagnostic performance of metagenomic next-generation sequencing (mNGS). Anti-MDA5+ DM patients who underwent mNGS or real-time PCR for PJP detection were recruited. The potential risk factors for PJP occurrence and death were analysed via Logistic regression and Cox proportional hazards regression, respectively. The diagnostic efficacy of mNGS was compared with the conventional methods. 91 patients were enrolled and 44 were assigned to PJP+ group. The PJP detection rate was 48.4%. PJP often occurred in the first 3 months (68.2%) of the disease; this period also showed the highest mortality rate (20.5%). Fever and increased lactate dehydrogenase (LDH) were independent risk factors for PJP occurrence, while trimethoprim-sulfamethoxazole (TMP/SMZ) prophylaxis was an independent protective factor (all P < 0.05). Older age and increased LDH were predictors for mortality in patients with anti-MDA5+ DM and PJP (all P < 0.05). In addition, we found that mNGS had a sensitivity of 100.0% and specificity of 90.0% in diagnosing PJP, with the highest area under the curve of 0.95 (P < 0.001). PJP has high prevalence and mortality in anti-MDA5+ DM. It is crucial for clinicians to identify high-risk patients and promptly institute TMP/SMZ to prevent PJP. mNGS is the preferred approach for pathogen detection in anti-MDA5+ DM when PJP is suspected.

Chen X ，Shu X ，He L ，Yang H ，Lu X ，Wang G ，Ge Y ... -  《-》

High incidence and mortality of Pneumocystis jirovecii infection in anti-MDA5-antibody-positive dermatomyositis: experience from a single center.

Idiopathic inflammatory myopathies (IIM) are associated with a significantly higher risk of opportunistic infections including Pneumocystis jirovecii pneumonia (PJP), a potentially fatal opportunistic infection. However, no prior studies have evaluated PJP infection in subtypes of IIM. To investigate the prevalence and mortality rate of PJP infection in subgroups of IIM patients stratified according to myopathy-specific antibodies. In the first part of the study, 463 consecutive patients with IIM were prospectively followed for a period of at least 1 year to analyze the incidence of PJP. In the second part of the study, we enrolled 30 consecutive PJP patients with any rheumatic disease in order to identify the mortality rate and risk factors by Cox regression analysis. The Kaplan-Meier method with log-rank testing was used to assess differences in survival. The prevalence of PJP in IIM patients was found to be 3.0/100 person-years, while in MDA5+ DM patients it was 7.5/100 person-years and in MDA5- IIM patients 0.7/100 person-years (P < 0.05). PJP typically occurred in the first 2 months in the case of MDA5+ DM patients who had a significant decrease in their CD4+ T cell counts and lymphocyte counts (P < 0.05). In PJP patients, 3-month mortality was higher for MDA5+ DM patients than in those with other rheumatic diseases (83.3% vs 38.9%, P < 0.05). Alarmingly, MDA5+ DM patients seemed not to benefit from prompt anti-PJP treatment, unlike patients with other rheumatic diseases whose survival improved when anti-PJP treatment was started within 6 days (P < 0.05). PJP has an alarming high incidence and mortality in MDA5+ DM patients. Timely treatment for PJP seems not to improve the prognosis of patients with this particular subtype. Hence, there remains a crucial unmet need to develop PJP prophylaxis for MDA5+ DM patients.

Huang L ，Fu Q ，Ye Y ，Lin Y ，Yan Q ，Chen S ... -  《-》

Clinical characteristics of and risk factors for Pneumocystis jirovecii pneumonia in anti-melanoma differentiation-associated gene 5 (Anti-MDA5) antibody-positive dermatomyositis patients: a single-center retrospective study.

Pneumocystis jirovecii pneumonia (PJP) is a serious opportunistic infection mainly diagnosed in patients with rheumatic conditions. However, PJP in anti-melanoma differentiation-associated gene 5-positive dermatomyositis (MDA5 + DM) patients remains poorly understood. We aimed to investigate the 6-month PJP risk in newly diagnosed MDA5 + DM patients. A retrospective observational study of 105 inpatients with newly diagnosed MDA5 + DM was conducted at Renji Hospital from January 2018 to November 2019. Demographic information, clinical characteristics, and treatment data were recorded. The primary outcome was PJP incidence within 6 months after a MDA5 + DM diagnosis. The analysis included 105 patients, including 13 patients diagnosed with PJP during the observation period. The median time from the MDA5 + DM diagnosis to PJP was 89 ± 38 days. Compared with the PJP - patients, the PJP + patients had a significantly greater risk of mortality (69.2% vs. 13.0% P < 0.001). Regarding the baseline comorbidities, hypertension (P = 0.013) and cancer (P = 0.02) were more common in the PJP + group. Additionally, a larger proportion of the PJP + patients received prolonged high-dose steroid therapy (≥ 60 mg/day and ≥ 1 month) (P = 0.022) and double or triple immunosuppressant therapy (P = 0.013). The multivariate analysis showed that PJP was independently associated with lymphopenia (ALC < 500 cells/µl) (OR: 5.434, 95% CI: 2.074-55.155; P = 0.012) and the combined use of cyclophosphamide (CTX) and tacrolimus (TAC) (OR: 10.695, 95% CI: 1.440-20.508; P = 0.005). There was a high incidence and mortality in the MDA5 + DM patients with PJP, with patients on combined immunosuppressive treatments, particularly CTX and TAC, being at a higher risk. Prolonged high-dose steroid therapy (≥ 60 mg/day and ≥ 1 month) was another risk factor for PJP. Key Points • There was a high incidence and mortality in the MDA5 + DM patients with PJP. • Most PJP cases occurred within 3 months after the MDA5 + DM diagnosis. • The 6-month infection risk of PJP increased with the administration of multiagent immunosuppression, especially the combination of CTX and TAC. • Prolonged high-dose steroid therapy (≥ 60 mg/day and ≥ 1 month) was another risk factor for PJP.

Li J ，Wang S ，Zheng J ，Li Q ，Li J ，Lu L ... -  《-》

Single-center retrospective analysis of Pneumocystis jirovecii pneumonia in patients after deceased donor renal transplantation.

To investigate the clinical features, early diagnosis, and treatment methods of Pneumocystis jirovecii pneumonia (PJP) after renal transplantation (RT). We retrospectively analyzed the clinical data of 80 patients with confirmed PJP who underwent RT between 2018 and 2021 in our hospital. In the present study, the incidence of PJP was 6.2% (80/1300). A 50% of cases (40 out of 80 patients) had developed a PJP infection during the first 6 months after RT and 81.3% (65 out of 80 patients) within 12 months. The median onset time of PJP was 6.5 months after RT. The most common symptom was fever (73.8%), followed by progressive dyspnea (51.3%) and dry cough (31.3%). In the initial phase of PJP, the most frequent CT finding was the presence of diffuse ground-grass shadows. In all, 27.5%, 37.5%, and 35% patients were diagnosed by induced sputum metagenomic next-generation sequencing (mNGS), peripheral blood mNGS, and characteristic clinical diagnostic features, respectively. The median 1,3-β-D-glucan level was 500 pg/mL, while the median C-reactive protein level was 63.4 mg/L. In most patients (83.8%), the procalcitonin levels were negative. The mean serum creatinine level was 171.9 ± 87.4 μmol/L. Of the 80 patients, 37 (46.2%) had coexisting cytomegalovirus (CMV) infection. All patients were treated with trimethoprim-sulfamethoxazole and third generation cephalosporin to prevent bacterial infection. The methylprednisolone dose (40-120 mg/d) varied according to illness. PJP usually occurs within 1 year after RT, typically within 6 months. Fever, dry cough, and progressive dyspnea are the most common clinical symptoms. PJP should be highly suspected if the patient has clinical symptoms and diffuse, patchy, ground-glass opacities on CT in both lungs after RT within 1 year. Peripheral blood or induced sputum mNGS is helpful for early diagnosis of PJP. Trimethoprim-sulfamethoxazole is still the first choice for the treatment of PJP. Combined use of caspofungin can reduce the dose and adverse reactions of trimethoprim-sulfamethoxazole in theory.

Zou J ，Wang T ，Qiu T ，Zhou J ，Chen Z ，Ma X ，Jin Z ，Xu Y ，Zhang L ... -  《-》

Risk factors associated with Pneumocystis jirovecii pneumonia in non-HIV immunocompromised patients and co-pathogens analysis by metagenomic next-generation sequencing.

Pneumocystis jirovecii pneumonia (PJP) is one of the most common opportunistic infections in immunocompromised patients. However, the accurate prediction of the development of PJP in non-HIV immunocompromised patients is still unclear. Non-HIV immunocompromised patients confirmed diagnosis of PJP by the clinical symptoms, chest computed tomography and etiological results of metagenomic next-generation sequencing (mNGS) were enrolled as observation group. Another group of matched non-HIV immunocompromised patients with non-PJP pneumonia were enrolled to control group. The risk factors for the development of PJP and the co-pathogens in the bronchoalveolar lavage fluid (BALF) detected by mNGS were analyzed.  RESULTS: A total of 67 (33 PJP, 34 non-PJP) participants were enrolled from Fujian Provincial Hospital. The ages, males and underlying illnesses were not significantly different between the two groups. Compared to non-PJP patients, PJP patients were more tends to have the symptoms of fever and dyspnea. The LYM and ALB were significantly lower in PJP patients than in non-PJP patients. Conversely, LDH and serum BDG in PJP patients were significantly higher than in non-PJP controls. For immunological indicators, the levels of immunoglobulin A, G, M and complement C3, C4, the numbers of T, B, and NK cells, had no statistical difference between these two groups. Logistic multivariate analysis showed that concomitant use of corticosteroids and immunosuppressant (OR 14.146, P = 0.004) and the lymphocyte counts < 0.7 × 109/L (OR 6.882, P = 0.011) were risk factors for the development of PJP in non-HIV immunocompromised patients. 81.82% (27/33) and 64.71% (22/34) mixed infections were identified by mNGS in the PJP group and non-PJP group separately. CMV, EBV and Candida were the leading co-pathogens in PJP patients. The percentages of CMV and EBV identified by mNGS in PJP group were significantly higher than those in the control group(p < 0.005).  CONCLUSIONS: Clinicians should pay close attention to the development of PJP in non-HIV immunocompromised patients who possess the risk factors of concomitant use of corticosteroids and immunosuppressant and the lymphocyte counts < 0.7 × 109/L. Prophylaxis for PJP cannot rely solely on CD4+ T counts in non-HIV immunocompromised patients. Whether CMV infection increases the risk of PJP remains to be further investigated.

Huang L ，Xu S ，Huang Z ，Chen Y ，Xu N ，Xie B ... -  《BMC Pulmonary Medicine》