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 ... -  《-》

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 ... -  《-》

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 ... -  《-》

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

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. 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. 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.

Hsu HC ，Chang YS ，Hou TY ，Chen LF ，Hu LF ，Lin TM ，Chiou CS ，Tsai KL ，Lin SH ，Kuo PI ，Chen WS ，Lin YC ，Chen JH ，Chang CC ... -  《-》

Compounded sulfamethoxazole improved the prognosis of dermatomyositis patients positive with anti-melanoma differentiation-associated gene 5.

Mortality of dermatomyositis patients positive with anti-melanoma differentiation-related gene 5 antibody (anti-MDA5-DM) is alarming, especially during the first several months. Infection is an important cause of early death. As there are no reports regarding the effect of prophylactic use of compounded sulfamethoxazole (coSMZ; each tablet contains 400 mg of sulfamethoxazole and 80 mg of trimethoprim) in anti-MDA5-DM patients, we conducted this study to evaluate the efficacy of coSMZ in reducing the incidence of Pneumocystis jirovecii pneumonia (PJP). Consecutive patients with new-onset anti-MDA5-DM from June 2018 to October 2021 in our centre were retrospectively reviewed for >12 months. They were divided into two groups-coSMZ and non-coSMZ-based on the initial use of prophylactic coSMZ. Mortality and the incidence of severe infection within 12 months were compared between two groups. Compared with the non-coSMZ group (n = 93), the coSMZ group (n = 121) had lower mortality (18.8% vs 51.1%; P < 0.001) and a lower incidence of PJP (6.8% vs 15.2%; P = 0.040) and fatal infection (16.1% vs 3.3%; P = 0.001) during the first 12 months from diagnosis. After adjusting for age, gender, disease duration, peripheral blood lymphocyte count, anti-MDA5 antibody titres, ground-glass opacity scores and treatments, an inverse association was revealed between the prophylactic use of coSMZ and incidence of PJP [adjusted odds ratio 0.299 (95% CI 0.102-0.878), P = 0.028]. Prophylactic use of coSMZ is an effective and safe way to improve the prognosis of anti-MDA5-DM patients by preventing the incidence of PJP.

Liu L ，Zhang Y ，Liu S ，Wang C ，Zhang L ，Guan W ，Zhang X ，Li W ，Shu X ，Li T ... -  《-》