A case of hypercalcemia from Pneumocystis jirovecii in an immunosuppressed non-HIV patient.

BACKGROUND: The prevalence of non-HIV related Pneumocystis jirovecii pneumonia (PJP) is increasing with use of immunosuppressive therapies. There are case reports of solid organ transplant recipients on immunosuppressive therapy presenting with mild hypercalcemia, leading to a diagnosis of PJP. Recent studies have shown efficacy of PJP prophylaxis for patients treated with rituximab with a favourable adverse effect profile. CASE PRESENTATION: A 78-year-old male with a history of PR3-ANCA vasculitis, chronic kidney disease and heart failure with reduced ejection fraction presented to our tertiary care hospital with a two-week history of confusion and non-productive cough. Background immunosuppression with rituximab was completed every six months. The patient was found to have hypercalcemia and new infiltrates and ground glass opacities on cross-sectional imaging. Bronchoscopy was performed that was positive for Pneumocystis jirovecii. He was treated with 21 days of trimethoprim-sulfamethoxazole and prednisone with resolution of symptoms and hypercalcemia. CONCLUSIONS: Herein, we present a novel case of PJP in a non-transplant recipient preceded by hypercalcemia. Our case demonstrates the importance for a high suspicion for PJP in chronically immunosuppressed patients on rituximab presenting with PTH-independent hypercalcemia.

Global prevalence, mortality, and main characteristics of HIV-associated pneumocystosis: A systematic review and meta-analysis.

The epidemiology of Human Immunodeficiency Virus (HIV)-associated pneumocystosis (HAP) is poorly described on a worldwide scale. We searched related databases between January 2000 and December 2022 for studies reporting HAP. Meta-analysis was performed using StatsDirect (version 2.7.9) and STATA (version 17) according to the random-effects model for DerSimonian and Laird method and metan and metaprop commands, respectively. Twenty-nine studies with 38554 HIV-positive, 79893 HIV-negative, and 4044 HAP populations were included. The pooled prevalence of HAP was 35.4% (95% CI 23.8 to 47.9). In contrast, the pooled prevalence of PCP among HIV-negative patients was 10.16% (95% CI 2 to 25.3). HIV-positive patients are almost 12 times more susceptible to PCP than the HIV-negative population (OR: 11.710; 95% CI: 5.420 to 25.297). The mortality among HAP patients was 52% higher than non-PCP patients (OR 1.522; 95% CI 0.959 to 2.416). HIV-positive men had a 7% higher chance rate for PCP than women (OR 1.073; 95% CI 0.674 to 1.706). Prophylactic (OR: 6.191; 95% CI: 0.945 to 40.545) and antiretroviral therapy (OR 3.356; 95% CI 0.785 to 14.349) were used in HAP patients six and three times more than HIV-positive PCP-negatives, respectively. The control and management strategies should revise and updated by health policy-makers on a worldwide scale. Finally, for better management and understanding of the epidemiology and characteristics of this coinfection, designing further studies is recommended.

[Role of glucocorticoids in pneumocystis pneumonia in patients with non-HIV infection/AIDS (HIV/AIDS) and related mechanisms].

Pneumocystis pneumonia (PCP) is an opportunistic infection caused by Pneumocystis carinii and is the most common fungal infection in HIV/AIDS patients. With the routine use of antiretroviral therapy (ART), the incidence of PCP infection in HIV/AIDS patients has decreased and the prognosis has improved significantly. On the other hand, the use of chemoradiotherapy and immunotherapy in patients with cancer, post-transplantation and autoimmune diseases are increasing dramatically, which has led to a similar increase in the incidence of PCP in these non-HIV/AIDS patients. There is a global shift in research on PCP from HIV-infected co-infected PCP (HIV-PCP) to non-HIV-infected co-infected PCP. The clinical course of non-HIV-PCP is rapid and severe, and the morbidity and mortality rates are higher than those of HIV-PCP. Studies have shown that 90% of non-HIV-PCP patients have a history of glucocorticoid use prior to infection, such as in patients with hematologic malignancies, solid organ transplants, and rheumatic diseases, and that long-term high-dose glucocorticoid use is an important risk for PCP susceptibility. Clinical practice has shown that PCP often occurs during the tapering of glucocorticoids, and a higher proportion of patients develop diffuse pulmonary lesions and, in more severe cases suffer from life-threatening acute respiratory failure. The pathogenesis of non-HIV infections associated with PCP is not yet clarified, and there is a lack of effective therapeutic practices that require further investigation.

Pulmonary Histoplasmosis in People Living with Human Immunodeficiency Virus in French Guiana: Clinical Epidemiology, Medical Imaging and Prognostic.

BACKGROUND: Histoplasmosis is mainly described as a disseminated disease in people living with HIV (PLHIV). Compared to historical descriptions in immunocompetent individuals, knowledge is lacking on the detailed clinical and radiological findings and outcomes of pulmonary histoplasmosis (PH). Overlooked or misdiagnosed with other AIDS-defining condition, prognostic of PLHIV may be at risk because of inappropriate care. METHODS: A retrospective multicentric study was conducted in PLHIV from French Guiana between January 1988 and October 2019. Proven PH were documented through mycological direct examination, culture, or histology. Patients with concomitant respiratory infections were excluded. RESULTS: Among 65 patients, sex ratio M:F was 2.4 with a median age of 39 years [IQR 25-75%: 34-44]. Median CD4 count was 24 cells/mm3 [11-71], with histoplasmosis as the AIDS-defining condition in 88% and concomitant AIDS-defining conditions in 29%. Clinical findings were fever (89%), cough (58%), dyspnea (35%), expectoration (14%), and hemoptysis (5%). Sixty-one X-rays and 24 CT-scans were performed. On X-rays, an interstitial lung disease was mainly found (77%). On CT-scans, a nodular pattern was predominant (83%): mostly miliary disease (63%), but also excavated nodules (35%). Consolidations were present in 46%, associated with miliary disease in 21%. Thoracic lymphadenopathies were found in 58%, mainly hilar and symmetric (33%). Despite antifungal treatment, case-fatality rate at one month was 22%. CONCLUSION: When faced with an interstitial lung disease on X-rays or a miliary pattern on CT-scans in advanced PLHIV, physicians in endemic areas, apart from tuberculosis or pneumocystosis, should include histoplasmosis as part of their differential diagnoses.

Coexistence of Cryptococcal Fungemia and Pneumocystis jirovecii Pneumonia in an HIV-Infected Patient: A Case Report.

INTRODUCTION: Opportunistic infections caused by bacteria and fungi are common in human immunodeficiency virus (HIV)-infected patients. Cryptococcus neoformans and Pneumocystis jirovecii are the most common opportunistic infections in immunosuppressed individuals, but their coexistence is rare. To our knowledge, this is the first case presented in Turkey involving the coexistence of C.neoformans fungemia and P.jirovecii pneumonia. CASE PRESENTATION: A 26-year-old male patient presented with a cachectic appearance, cough, sputum, weakness, shortness of breath, and a weight loss of 15 kg in the last three months. It was learned that the patient was diagnosed with HIV three years ago, did not go to follow-ups, and did not use the treatments. CD4 cell count was 7/mm3 (3.4%), CD8 cell count was 100 (54%) mm3, and HIV viral load was 5670 copies/mL. In thorax computed tomography (CT), increases in opacity in diffuse ground glass density in both lungs and fibroatelectasis in lower lobes were observed. With the prediagnosis of P. jiroveci pneumonia, the HIV-infected patient was given trimethoprim-- sulfamethoxazole 15 mg/kg/day intravenously (i.v.). On the 4th day of the patient's hospitalization, mutiplex PCR-based rapid syndromic Biofire (Film Array) blood culture identification 2 (BCID2) test (Biomerieux, France) was applied for rapid identification from blood culture. C. neoformans was detected in the blood culture panel. The treatment that the patient was taking with the diagnosis of C. neoformans fungemia was started at a dose of liposomal amphotericin B 5 mg/kg/- day + fluconazole 800 mg/day. CONCLUSION: While the incidence of opportunistic infections has decreased with antiretroviral therapy (ART), it remains a problem in patients who are unaware of being infected with HIV or who fail ART or refuse treatment. High fungal burden, advanced age, low CD4+ cell count, and being underweight are risk factors for mortality in HIV-positive patients. Our case was a cachectic patient with a CD4 count of 7 cells/mm3. Despite the early and effective treatment, the course was fatal.

Pneumocystis jirovecii pneumonia in intensive care units: a multicenter study by ESGCIP and EFISG.

BACKGROUND: Pneumocystis jirovecii pneumonia (PJP) is an opportunistic, life-threatening disease commonly affecting immunocompromised patients. The distribution of predisposing diseases or conditions in critically ill patients admitted to intensive care unit (ICU) and subjected to diagnostic work-up for PJP has seldom been explored. MATERIALS AND METHODS: The primary objective of the study was to describe the characteristics of ICU patients subjected to diagnostic workup for PJP. The secondary objectives were: (i) to assess demographic and clinical variables associated with PJP; (ii) to assess the performance of Pneumocystis PCR on respiratory specimens and serum BDG for the diagnosis of PJP; (iii) to describe 30-day and 90-day mortality in the study population. RESULTS: Overall, 600 patients were included in the study, of whom 115 had presumptive/proven PJP (19.2%). Only 8.8% of ICU patients subjected to diagnostic workup for PJP had HIV infection, whereas hematological malignancy, solid tumor, inflammatory diseases, and solid organ transplants were present in 23.2%, 16.2%, 15.5%, and 10.0% of tested patients, respectively. In multivariable analysis, AIDS (odds ratio [OR] 3.31; 95% confidence interval [CI] 1.13-9.64, p = 0.029), non-Hodgkin lymphoma (OR 3.71; 95% CI 1.23-11.18, p = 0.020), vasculitis (OR 5.95; 95% CI 1.07-33.22, p = 0.042), metastatic solid tumor (OR 4.31; 95% CI 1.76-10.53, p = 0.001), and bilateral ground glass on CT scan (OR 2.19; 95% CI 1.01-4.78, p = 0.048) were associated with PJP, whereas an inverse association was observed for increasing lymphocyte cell count (OR 0.64; 95% CI 0.42-1.00, p = 0.049). For the diagnosis of PJP, higher positive predictive value (PPV) was observed when both respiratory Pneumocystis PCR and serum BDG were positive compared to individual assay positivity (72% for the combination vs. 63% for PCR and 39% for BDG). Cumulative 30-day mortality and 90-day mortality in patients with presumptive/proven PJP were 52% and 67%, respectively. CONCLUSION: PJP in critically ill patients admitted to ICU is nowadays most encountered in non-HIV patients. Serum BDG when used in combination with respiratory Pneumocystis PCR could help improve the certainty of PJP diagnosis.

Rapidly progressive interstitial lung disease combined with pneumocystis jiroveci pneumonia in a patient with single anti-TIF-1γ antibody positive dermatomyositis in the context of an underlying tumor.

BACKGROUND: Interstitial lung disease (ILD) is a frequently observed comorbidity in autoimmune diseases such as dermatomyositis/polymyositis (DM/PM), and it is significantly associated with specific autoantibody types. One unique antibody type is the anti-transcription intermediate factor-1γ antibody (anti-TIF-1γ Ab), which has a positive rate of only 7%. It is often found in combination with malignancy and rarely with ILD, particularly rapidly progressive ILD (RPILD). In some cases, the presence of ILD in individuals with DM may indicate a paraneoplastic syndrome. Pneumocystis jiroveci pneumonia (PJP) typically occurs due to intensive immunosuppressive therapy, human immunodeficiency virus (HIV) infection, or malignancy, and rarely as an isolated condition. CASE PRESENTATION: A 52-year-old man with a history of rapid weight loss but non-HIV infected and not immunosuppressed who presented with fever, cough, dyspnea, weakness of the extremities, characteristic rash and mechanic's hand. Pathogenic tests suggested PJP, laboratory tests suggested a single anti-TIF-1γ Ab positive DM, imaging suggested ILD, and pathology revealed no malignancy. RPILD and acute respiratory distress syndrome (ARDS) developed after anti-infection and steroid hormone therapy. After mechanical support therapy such as Extracorporeal Membrane Oxygenation (ECMO), the patient developed late-onset cytomegalovirus pneumonia (CMVP), complicated bacterial infection, and ultimately death. Additionally, we discuss the potential causes of rapid weight loss, the mechanisms by which anti-TIF-1γ Ab may lead to ILD, and the possible connection between anti-TIF-1γ Ab positivity, rapid weight loss, immune abnormalities, and opportunistic infections. CONCLUSIONS: This case emphasizes the importance of early recognition of malignant tumors and pulmonary lesions, assessment of the body's immune status, prompt initiation of immunosuppressive treatment, and prevention of opportunistic infections in individuals with single anti-TIF-1γ Ab positive DM presenting with rapid weight loss.

Trimethoprim-Sulfamethoxazole-associated early neutropenia in Mexican adults living with HIV: A cohort study.

INTRODUCTION: Trimethoprim/sulfamethoxazole (TMP/SMX) is the antimicrobial of first choice in the treatment and prophylaxis of Pneumocystis jirovecii pneumonia (PCP) in immunocompromised patients, particularly in people living with human immunodeficiency virus (HIV). TMP/SMX use entails different adverse effects, and its association with early neutropenia is minimally documented. This study aimed to identify the risk of early neutropenia associated with TMP/SMX use in adults living with HIV in Mexico. METHODS: A prospective cohort study was conducted in TMP/SMX-naïve adults living with HIV admitted to a third-level hospital between August 2019 and March 2020. Socio-demographic, clinical, and laboratory data were collected. According to patients' diagnostic, if they required treatment or prophylaxis against PCP, medical staff decided to prescribe TMP/SMX, as it is the first-line treatment. The risk of TMP/SMX induced early neutropenia, as well as associated factors were analyzed through a bivariate model and a multivariate Poisson regression model. The strength of association was measured by incidence rate ratio (IRR) with 95% confidence interval. RESULTS: 57 patients were enrolled in the study, of whom 40 patients were in the TMP/SMX treatment-group for treatment or prophylaxis of PCP (204.8 person-years of observation, median 26.5 days) and 17 patients were in the non-treatment group because they did not need the drug for treatment or prophylaxis of PCP (87.0 person-years of observation, median 21 days). The incidence rate of early neutropenia in the TMP/SMX-treatment group versus non-treatment group was 7.81 and 1.15 cases per 100 person-years, respectively. After adjusting for stage 3 of HIV infection and neutrophil count <1,500 cells/mm3 at hospital admission, the current use of TMP/SMX was not associated with an increase in the incidence rate ratio of early neutropenia (adjusted IRR: 3.46; 95% CI: 0.25-47.55; p = 0.352). CONCLUSIONS: The current use of TMP/SMX in Mexican adults living with HIV was not associated with an increase in the incidence rate ratio of early neutropenia.

Impact of pneumocystosis on the Spanish health care system, 1997-2020: Profile of HIV and non-HIV immunocompromised patients.

BACKGROUND: Pneumocystis jirovecii is an opportunistic fungus recognized for causing P. jirovecii pneumonia. The global prevalence is thought to be higher than 400,000 annual cases, although detailed information about epidemiological patterns is scarce. METHODOLOGY: A retrospective longitudinal descriptive study was performed among patients with diagnosis of pneumocystosis according to Classification of Diseases 9th edition, Clinical Modification (code 136.3 for the cases from 1997 to 2015; and 10th edition code B59.0 for cases from 2016 to 2020 in Spanish public hospitals from 1 January 1997-31 December 2020. RESULTS: A total of 25289 cases were diagnosed. The period incidence rate was 2.36 (95 % CI, 2.33-2.39) cases per 100,000 person-years. Infection was more frequent among men (72.2 %) than among women (27.8 %). Comorbidity was the main characteristic of this cohort. Up to 72.3 % of pneumocystis-infected patients (18293) had HIV coinfection. During the study period, there was a progressive decrease in the number of HIV coinfected cases as the group of patients without HIV infection increased, with the largest group in 2017. The lethality rate in the cohort was 16.7 %. The global cost was €229,234,805 and the average ( ± SD) cost per patient was €9065 ( ± 9315). CONCLUSIONS: The epidemiology of pneumocystosis in Spain has changed in the last two decades. We noted in our study the possibility of a reemergence among non-HIV immunocompromised patients as patients with hematological and nonhematological neoplasia and other risk groups. The lethality of pneumocystosis continues to be high, and the underlying diseases are the main variable associated with lethality.

No long-term effect of past Pneumocystis jirovecii pneumonia on pulmonary function in people with HIV.

OBJECTIVE: To assess the impact of past Pneumocystis jirovecii pneumonia (PJP) on the pulmonary diffusion capacity in people with HIV (PWH) with a history of advanced immunodeficiency. DESIGN: Prospective cross-sectional study. METHODS: Adult PWH with past PJP >1 year ago were included as the study group. The control group consisted of PWH with a nadir CD4 + lymphocyte count <200 cells/mm 3 , matched by age, sex, smoking status and time since HIV diagnosis. All PWH completed a pulmonary function test (PFT) consisting of pre-bronchodilation spirometry, body plethysmography and single-breath carbon monoxide transfer factor (TLCO) measurement. TLCO, diffusion impairment (defined as a TLCO Z -score <-1.645), total lung capacity (TLC) and forced expiratory volume in one second/forced vital capacity (FEV1/FVC) Z -scores were assessed. Multivariable regression analyses were conducted with Z -scores and odds of diffusion impairment as outcomes. RESULTS: PFTs of 102 participants were analyzed, 51 of whom had past PJP with a median of 10 years since PJP. Mean TLCO Z -score and diffusion impairment rate did not differ significantly between groups ( P  = 0.790; P  = 0.650). Past PJP was not independently associated with TLCO Z -score [ ß = 0.14; 95% confidence interval (CI) -0.30-0.57], diffusion impairment (odds ratio 1.00; 95% CI 0.36-2.75) nor TLC or FEV1/FVC Z -scores, whereas current (vs. never) smoking was associated with more diffusion impairment and lower TLCO Z -scores. CONCLUSION: In our study, past PJP was not associated with long-term diffusion impairment. Our findings suggest that smoking plays a more important role in persistent pulmonary function impairment whereas PJP-related changes seem to be reversible.

Extrapulmonary Pneumocystis jirovecii infection in an advanced HIV-infected patient: A case report and literature review.

BACKGROUND: Pneumocystis jirovecii infection is the most common opportunistic infection that causes pneumonia in human immunodeficiency virus (HIV)-infected patients; however, extrapulmonary P. jirovecii infection is extremely rare after the use of antiretroviral therapy. Here, we present the second reported case of paraspinal mass caused by P. jirovecii infection in an advanced HIV-infected patient. CASE PRESENTATION: A 45-year-old woman presented with dyspnea on exertion, and significant weight loss within the preceding 4 months. Initial complete blood count (CBC) findings revealed pancytopenia with a hemoglobin (Hb) level of 8.9 g/dL, a white blood cell (WBC) count of 2180 cells/mm3 with 68% neutrophils, and a platelet count of 106,000 cells/mm3. Anti-HIV was positive with an absolute cluster of differentiation 4 (CD4) count of 16 cells/ mm3. A computed tomography scan of the chest revealed an enhancing soft tissue mass-like lesion at the right paravertebral region (T5-T10 level) and a thick-walled cavity lesion at the left lower lung. A CT-guided biopsy of the paravertebral mass was performed and histopathology revealed granulomatous inflammation consisting of dense aggregates of epithelioid cells and macrophages, and scattered foci of pink foamy to granular materials amidst the granulomatous inflammation. Gomori methenamine silver (GMS) staining revealed thin cystic-like structures (ascus) that were observed to be morphologically consistent with P. jirovecii. Molecular identification and DNA sequencing from the paraspinal mass was 100% identical to P. Jirovecii. The patient was successfully treated with oral trimethoprim-sulfamethoxazole for 3 weeks and antiretroviral therapy (ART) with tenofovir (TDF), lamivudine (3TC), and dolutegravir (DTG). A follow-up CT scan of the chest at 2 months after treatment showed a decrease in sizes of both the paravertebral mass and the cavitary lung lesion. CONCLUSIONS: Extrapulmonary pneumocystosis (EPCP) has become an extremely rare condition in HIV-infected patients after the widespread use of ART. EPCP should be considered in ART-naive HIV-infected patients suspected of having or diagnosed with Pneumocystis jirovecii pneumonia who present with atypical symptoms and/or signs. Histopathologic examination with GMS staining of affected tissue is necessary for the diagnosis of EPCP.

Rare Co-Infection of the Lungs with EBV and Pneumocystis Carinii in a Patient with Kidney Cancer: a Case Report.

BACKGROUND: Epstein-Barr virus (EBV) is the primary agent of infectious mononucleosis, lymphoma, and naso-pharyngeal carcinoma, but rarely involves the lungs. Pneumocystis carinii is commonly found in patients with HIV infection and is not pathogenic when the host is healthy, but opportunistic infections can occur when the body is immunocompromised, causing pneumocystis pneumonia (PCP). It is rare for both diseases to occur in the lungs of the same patient. METHODS: Next-generation sequencing (NGS), laboratory examination, chest CT scan, electronic bronchoscopy, and pathogenetic examination were used in this study. RESULTS: Laboratory tests showed (1-3)-ß-D-glucan of 889.47 pg/mL, negative human immunodeficiency virus (HIV) antibody, and negative Aspergillus immunological test. Chest CT showed multiple high-density shadows in both lungs, and EBV infection combined with Pneumocystis carinii pneumonia was confirmed by bronchoscopic biopsy and NGS examination. CONCLUSIONS: Elevated serum (1-3)-ß-D-glucan is not a specific index for infectious diseases. Bronchoscopy and the NGS has high specificity in pathogen detection of infectious diseases.

Pneumocystis pneumonia in a patient with diabetes mellitus: A case report.

RATIONALE: Pneumocystis pneumonia (PCP) is an opportunistic infection of patients with congenital or acquired immunodeficiency. It is most frequently occurred in human immunodeficiency virus (HIV) infection, organ transplantation, leukemia, and immunosuppressive therapy. Here we describe the rare case of PCP in a non-HIV-infected diabetic patient and find possible reasons for the association through a literature review. PATIENT CONCERNS: A 65-years-old male was admitted to our hospital due to a 10-year history of abnormal blood glucose levels and edema of both lower extremities for half a month. However, the patient developed a high fever and progressive dyspnea during hospitalization. DIAGNOSES: The patient had elevated blood sugar levels, a low white blood cell count within normal limits, and severe lymphopenia. His blood G test and lactate dehydrogenase levels increased significantly. Multiple sputa and bronchoalveolar lavage fluid specimens for Pneumocystis jirovecii (PJ) nucleic acid detection were positive. Chest computed tomography scan demonstrated hazy patchy shadows in the lungs suspected to be pulmonary infections. No tumor, transplantation, or an autoimmune disease was found in the examinations. The patient was diagnosed with PCP finally. INTERVENTIONS: A combination of oral trimethoprim-sulfamethoxazole and intravenous caspofungin was administered immediately against PJ. The patient was also treated with noninvasive ventilator-assisted ventilation, subcutaneous insulin, and hemodialysis therapy. OUTCOMES: The patient was discharged home finally with a fair general condition and was followed up without respiratory symptoms. LESSONS: The compromised immunity in HIV-negative patients with diabetes may be related to lymphocyte decrease and dysfunction, which may cause diabetic patients prone to PJ. Although PCP is rare in diabetes, it should be paid attention to the high rate of misdiagnosis and missed diagnosis.

A Case of Pneumocystis jirovecci in a Patient with Non-Small Cell Lung Cancer Treated with Immunotherapy.

Immune checkpoint inhibitors have become the standard of care in the management of metastatic non-small cell lung cancer (NSCLC) and are associated with improved outcomes when compared to traditional chemotherapy regimens. However, they present with their own unique set of immune-related side effects. One immune-related adverse effect that can arise is pneumonitis, where patients present with dyspnea with nonspecific radiologic findings, making it challenging to differentiate from other etiologies causing dyspnea. We present a case of a 58-year-old woman with NSCLC previously treated with immunotherapy, who presented with shortness of breath. She was initially thought to have immune-related pneumonitis and was treated with immunosuppressive therapy. After several days of treatment, bronchoscopy demonstrated a positive polymerase chain reaction (PCR) for Pneumocystis jirovecii (PJP) after an initial negative direct fluorescent antibody (DFA). The patient was started on appropriate management for PJP and no further immunosuppressive therapy was given.

Pneumocystis jiroveci Pneumonia secondary to tyrosine kinase inhibitor with blinatumomab therapy: A case report.

BACKGROUND: Pneumocystis jiroveci Pneumonia (PCP) is a common cause of opportunistic lung infection and is associated with high mortality in immunocompromised patients. Few reports describe pneumocystis jiroveci as a causative agent of tyrosine kinase inhibitor or blinatumomab related infections. Case presentation A 64-year-old man with philadelphia chromosome positive acute lymphoblastic leukemia (ALL) presented to the intensive care unit with intermittent high fever and shortness of breath. Three cycles of tyrosine kinase inhibitor (TKI) with blinatumomab therapy were given in recent 4 months. Next-generation sequencing of bronchoalveolar lavage fluid and peripheral blood showed pneumocystis jiroveci. After trimethoprim- sulfamethoxazole treatment and subsequent mechanical ventilation, the infection was controlled successfully. CONCLUSION: Due to susceptibility and early onset of PCP in ALL patients received TKI combined with blinatumomab therapy, so we should be alert to PCP when pulmonary infection occurred.

Pneumocystis pneumonia in patients with Cushing's syndrome: A French multicenter retrospective study.

OBJECTIVE: Pneumocystis pneumonia (PcP) is an opportunistic infection occurring in immunocompromised patients. Cushing's syndrome (CS) impairs the immune system, and several authors have reported PcP in patients with CS. The present study aimed to characterize PcP occurring in a CS context and its management in French tertiary centers, in order to highlight the similarities in clinical presentation and treatment according to whether prophylaxis is implemented or not. METHODS: This was a multicenter retrospective study conducted in several French University Hospitals and Cancer Centers. Patients with PcP and confirmed CS regardless of etiology were included. We excluded patients with other known causes of acquired immunodeficiency with increased risk of PcP. RESULTS: Twenty-five patients were included. CS etiology was neoplastic in 84.0% of cases. CS clinical presentation associated predominant catabolic signs (76.0%), hypokalemia (91.7%) and lymphopenia (89.5%). CS was intense in most patients, with mean plasma cortisol levels at diagnosis of 2.424±1.102nmol/L and urinary free cortisol>10× the upper limit of normal in 85.0%. In all patients, PcP onset followed introduction of cortisol blockers, at a median 5.5 days. Patients were treated with 1 to 3 cortisol blockers, mainly metyrapone (88%), which significatively lowered plasma cortisol levels to 667±541nmol/L at the onset of PcP (P<0.001). PcP occurred in 7 patients despite prophylaxis. Finally, 60.0% patients were admitted to intensive care, and 20.0% died of PcP. CONCLUSION: High mortality in patients with PcP implies that clinicians should be better informed about this rare infectious complication. Prophylaxis remains controversial, requiring comparative studies.

Infectious complications in adult patients with idiopathic minimal change nephrotic syndrome undergoing immunosuppressive therapy.

BACKGROUND: Patients with idiopathic minimal change nephrotic syndrome (MCNS) undergoing immunosuppressive therapy are susceptible to infectious complications. Study specifically focusing on adult population's infectious complications is lacking. METHODS: We retrospectively collected 101 adult patients with biopsy-proven idiopathic MCNS and analysed for the infectious complications. Published literatures were also reviewed aiming to evaluate the feasibility of prophylactic antibiotic treatment. RESULTS: Infectious complications developed in 17 of 101 (16.8%) patients, with pneumonia (n = 4), cellulitis/fasciitis (n = 4) and urinary tract infection (UTI) (n = 4) being the dominant diseases, and Gram-negative bacilli the main cause. AKI stage ≥2 (Hazard ratio = 6.1; 95% CI: 1.2-31.9, p = 0.031) and non-remission by treatment (Hazard ratio = 4.4; 95% CI: 1.2-15.6, p = .023) were the two independent risk factors relevant to developing infectious complications. Review of 16 published literatures and our data showed that even no prophylactic antibiotic therapy, only one case of Pneumocystis jirovecii pneumonia developed among the 1787 accumulative cases of MCNS. In contrast, 16 (44%) of acute flare cases were reported among the 36 patients with positive hepatitis B surface antigen that did not receive antiviral prophylactic therapy. CONCLUSIONS: Advanced acute kidney injury and non-remission by treatment are the risk factors toward developing infectious complications in adult MCNS undergoing immunosuppressive therapy. It appears unnecessary to use prophylactic antibiotic for Pneumocystis jirovecii pneumonia or other bacterial infections, while screening and prophylactic therapy for hepatitis B and latent tuberculosis are critical for patients in prevalent area.

Pneumocystis jirovecii Pneumonia Associated with COVID-19 in Patients with Interstitial Pneumonia.

Here, we report two cases of patients with interstitial pneumonia (IP) on steroids who developed Pneumocystis jirovecii pneumonia (PJP) following coronavirus disease 2019 (COVID-19) infection. Case 1: A 69-year-old man on 10 mg of prednisolone (PSL) daily for IP developed new pneumonia shortly after his COVID-19 infection improved and was diagnosed with PJP based on chest computed tomography (CT) findings and elevated serum ß-D-glucan levels. Trimethoprim-sulfamethoxazole (TMP-SMZ) was administered, and the pneumonia resolved. Case 2: A 70-year-old woman taking 4 mg/day of PSL for IP and rheumatoid arthritis developed COVID-19 pneumonia, which resolved mildly, but her pneumonia flared up and was diagnosed as PJP based on CT findings, elevated ß-D-glucan levels, and positive polymerase chain reaction for P. jirovecii DNA in the sputum. The autopsy revealed diffuse alveolar damage, increased collagen fiver and fibrotic foci, mucinous component accumulation, and the presence of a P. jirovecii cyst. In conclusion, steroids and immunosuppressive medications are well-known risk factors for PJP. Patients with IP who have been taking these drugs for a long time are frequently treated with additional steroids for COVID-19; thus, PJP complications should be avoided in such cases.

Pneumocystis jirovecii-associated immune reconstitution inflammatory syndrome-like phenomenon in a child with leukaemia: a case report and literature review.

BACKGROUND: Immune reconstitution inflammatory syndrome (IRIS) refers to the phenomenon of intense immune responses against pathogens in patients with AIDS undergoing antiretroviral therapy to reconstitute immune function, resulting in functional impairment of multiple organs. Non-AIDS immunosuppressed hosts may also develop similar manifestations to IRIS during immune recovery. CASE PRESENTATION: An 8-year-old girl presented with acute lymphoblastic leukaemia was admitted for scheduled chemotherapy treatment. During chemotherapy, she experienced pancytopenia and Pneumocystis jirovecii pneumonia, which was diagnosed based on the abnormal shadows observed on chest computed tomography, the elevation of serum ß-D-glucan, and the positive mNGS results of Pneumocystis jirovecii in both sputum and blood. After treatment with Granulocyte Colony-Stimulating Factor, sulfamethoxazole, and caspofungin, aggravation of lung lesions was discovered and severe interstitial lung disease developed in a short period along with a rapidly increasing leukocyte count. Intravenous methylprednisolone pulse therapy was given, but lung function did not improve, and she finally died after the withdrawal of medical care. CONCLUSIONS: For patients with acute lymphocytic leukaemia infected with Pneumocystis jirovecii, the rapid aggravation of pulmonary lesions in the process of blood recovery and immune reconstitution should raise vigilance against the possibility of IRIS-like reactions. The use of granulocyte stimulating factors may aggravate the inflammatory response in the lungs. The timing, dosage, and duration of treatment of glucocorticoids and the impact of high-dose methylprednisolone pulse therapy on the prognosis of patients should be explored in further research.