scholarly journals Invasive fungal infections in children with rheumatic diseases

2021 ◽  
Vol 12 (5) ◽  
pp. 48-55
Author(s):  
O. P. Kozlova ◽  
M. M. Kostik ◽  
M. D. Kuznetsova ◽  
M. F. Dubko ◽  
L. S. Snegireva ◽  
...  
Keyword(s):  
Risk Factors ◽  
Invasive Aspergillosis ◽  
Rheumatic Diseases ◽  
Invasive Candidiasis ◽  
Lupus Erythematosus ◽  
Fungal Infections ◽  
Immunosuppressive Agents ◽  
Severe Neutropenia ◽  
Systemic Rheumatic Diseases ◽  
Invasive Mycoses

Introduction. In children with rheumatic diseases, severe fungal infections (invasive mycoses – IM) are not well understood.Objectives. To analyze risk factors, disease course of IM in children with systemic rheumatic diseases.Materials and methods. For diagnosis of IM were used criteria EORTC/MSGERC, 2019. We reviewed the literature over the past 15 years on IM in children with rheumatic diseases from the international databases Pubmed and Web of Science.Results. In retrospective multicenter study were included 8 children with IM and systemic rheumatic diseases: ANCA-associated vasculitis (n=4), systemic lupus erythematosus (n=3), juvenile rheumatoid arthritis (n=1). Median age was 13,5 (8-17) y., boys – 67%. Invasive aspergillosis was diagnosed in 5 patients and invasive candidiasis – 3. The risk factors of invasive mycoses were high rheumatic disease activity (100%), corticosteroids (prednisolone ≥ 0,3 mg/kg/d) use for ≥21 d (87,5%), immunosuppressive therapy (87,5%), recent (≤ 2 weeks) pulse steroid therapy (75%), hemophagocytic lymphohistiocytosis (62,5%), prolonged (≥ 10 days) severe neutropenia (≤ 0,5х109/l) (62,5%), and prolonged (≥10 days lymphopenia (≤ 1,0х109/l) (37,5%). In patients with invasive aspergillosis the involved organ was the lung, in patients with invasive candidiasis a candidemia was diagnoses. All patients received antifungal therapy. The overall 30 days survival rate was 37,5%.Сonclusions. Children with high rheumatic diseases activity and intensive treatment with immunosuppressive agents should be considered as patients with a high risk of invasive mycoses with a high mortality. 

A New Risk Score for Invasive Aspergillosis in Patients with Haematological Malignancies.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1469-1469
Author(s):  
Marta Stanzani ◽  
Mauro Fiacchini ◽  
Fabio Tumietto ◽  
Pierluigi Viale ◽  
Michele Baccarani ◽  
...  
Keyword(s):  
Risk Factors ◽  
Invasive Aspergillosis ◽  
Risk Score ◽  
Haematological Malignancy ◽  
Fungal Infections ◽  
Chronic Gvhd ◽  
Smoking Habit ◽  
Univariate Analysis ◽  
Severe Neutropenia ◽  
Haematological Malignancies

Abstract Invasive fungal infections, particularly invasive aspergillosis (IA), are frequent complications in immunocompromised patients. The identification of risk factors for IA is crucial to select patients who will benefit from different antifungal treatment. Retrospectively, we studied 1,194 hospitalizations registered at our Institution between March 2005 and December 2007, involving 618 patients affected by haematological malignancies (acute leukemia 34%, lymphoma 34%, multiple myeloma 24%, chronic myeloid leukemia 5%, severe aplastic anemia 1.5%, chronic lymphocytic leukemia 1.5%), with the purpose of developing a risk score able to stratify patients in categories at different risk for IA. Every febrile episode and every hospitalization without febrile episodes were recorded as single “phase”, for a total number of 1,409 “phases”. In 53% of the phases, the haematological malignancy was fully active (first presentation or resistant disease), and the main treatments administrated were: induction chemotherapy (18%), consolidation chemotherapy (20%), salvage chemotherapy (15%), HSCT in 33% (autologous: 21%; allogeneic: 12%). In 13% of the hospitalizations, patients did not receive chemotherapy but supportive cares. Seventeen variables were assessed as risk factors for IA according to literature data and to local clinical practice (age, smoking habit, type of job, previous IA, prolonged steroids treatment, diabetes, type of haematological malignancy, disease staus, type of treatment, prolonged neutropenia and lymphocytopenia, acute or chronic GvHD, CMV infection, mucositis, presence or absence of HEPA filter, proximity of building sites to the Haematology Unit) receiving a score ranging from 0 to 2. Summing the weighted points assigned to each variable, a total score (TSCORE08) was calculated for each phase and allowed to empirically identify 3 groups of patients at low (1 to 8), intermediate (8.5 to 11.5), and high (12 to 17) risk for IA, and was significantly higher in patients with IA (p < 0.001). Nine variables resulted to correlated significantly with IA in univariate analysis and were entered into the logistic regression analysis and 4 of them (type of job, lymphocytopenia, disease status, prolonged severe neutropenia) maintained their prognostic significance, allowing to derive, for each phase, a new score (BoSCORE08), which was also significantly higher in patients with IA (p < 0.001). The Areas Under the Curve derived from the TSCORE08 and the BoSCORE08 were equivalent, but the BoSCORE08 significantly reduced the number of variables taken into consideration. Adopting 5 as cut-off value for BoSCORE08, the model showed a high Negative Predictive value, a sensitivity of 0.950 (38/40) and a specificity of 0.545 (623/1,369), with a diagnostic Odds Ratio of around 22, which indicates that the risk of experiencing an IA in a patient with high BoSCORE08 was around 22 times higher than that of a patient with a low BoSCORE08. In conclusion, BoSCORE08 may contribute to optimize the management of patients at high risk for IA, improving the outcome, reducing the toxicity and the costs related to the use of antifungal agents in patients with haematological malignancies.

Invasive aspergillosis in adult patients with rheumatic diseases

2020 ◽  
Vol 14 (4) ◽  
pp. 16-22
Author(s):  
V. I. Mazurov ◽  
A. M. Lila ◽  
O. V. Shadrivova ◽  
M. S. Tonkoshkur ◽  
M. S. Shostak ◽  
...  
Keyword(s):  
Risk Factors ◽  
Respiratory Failure ◽  
Invasive Aspergillosis ◽  
Rheumatic Diseases ◽  
Lupus Erythematosus ◽  
Clinical Manifestations ◽  
Underlying Disease ◽  
Control Group ◽  
Group 2 ◽  
Group 1

Objective: to study risk factors for invasive aspergillosis (IA), its etiology, clinical manifestations, and treatment efficiency in patients with rheumatic diseases (RD).Patients and methods. The first study of proven and probable IA (EORT/MSGERC, 2019) was conducted in 18 patients with RD, who accounted for 3% of all adult IA patients (n=699) included in the 1998–2020 registry of the Department of Clinical Mycology, Allergology, and Immunology, I.I. Mechnikov North-Western State Medical University (Group 1). This group comprised 56% women; the median age was 59 [21; 75] years. Group 2 (a comparison group) included 610 adult hematology patients with IA (median age, 45 [18; 79] years; 42% women). A prospective case-control study was conducted to identify risk factors for IA in patients with RD: 36 rheumatic patients without IA (median age, 58 (18–79) years; 61% women) (a control group).Results and discussion. Patients with RD were found to often develop IA in the presence of anti-neutrophilic cytoplasmic antibody-associated vasculitis (granulomatosis with polyangiitis and microscopic polyangiitis) and systemic lupus erythematosus (50 and 16%, respectively). It was shown for the first time that the likelihood of IA in patients with RD increases with prolonged (median 14 days) lymphocytopenia during RD treatment (odds ratio 13.0; 95% confidence interval, 3.3–50.3). The main causative agents of IA were A. fumigatus (50%) and A. niger (29%). IA was more severe in Group 1 than in Group 2: in the resuscitation and intensive care units, there were 44 and 18%, respectively (p=0.01). Group 1 versus Group 2 more frequently had respiratory failure (61 and 37%, respectively; p=0.03), hemoptysis (28 and 7%; p=0.0001), chest pain (17 and 7%; p=0.04), and cardiac involvement (11 and 1%; p=0.0001), and less frequently had fever (67 and 85%; p=0.01). The common site of IA was the lung (83%); the characteristic feature detected by computed tomography (CT) is pulmonary cavitation (44%). Antifungal therapy was used in 89% of Group 1 patients; the overall 12-week survival was 69%.Conclusion. In patients with RD, it is difficult to differentiate between the progression of the underlying disease, adverse drug reactions, infectious complications, or a combination of these disorders due to the similarity of their clinical manifestations. When RD patients with infectious syndrome and respiratory failure develop prolonged lymphocytopenia during combination therapy, AI should be suspected and lung CT, bronchoscopy, and mycological examination of the material obtained by bronchoalveolar lavage be done.

scholarly journals AB0507 INVASIVE ASPERGILLOSIS IN ADULT RHEUMATOLOGICAL PATIENTS IN SAINT PETERSBURG, RUSSIA.

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1551.1-1552
Author(s):  
V. Mazurov ◽  
O. Shadrivova ◽  
M. Shostak ◽  
L. Martynova ◽  
M. Tonkoshkur ◽  
...  
Keyword(s):  
Risk Factors ◽  
Systemic Lupus Erythematosus ◽  
Renal Failure ◽  
Invasive Aspergillosis ◽  
Lupus Erythematosus ◽  
Granulomatosis With Polyangiitis ◽  
Control Group ◽  
Systemic Lupus ◽  
Anca Associated Vasculitis ◽  
Underlying Diseases

Background:Invasive aspergillosis (IA) is a severe opportunistic infection that is not well understood in rheumatological patients.Objectives:To study risk factors, etiology, clinical manifestations and results of treatment of IA in adult rheumatological patients.Methods:Retrospective analysis of 830 patients (1998-2019) with “proven” and “probable” IA (EORTC / MSG, 2019), adults - 699 (84%). The main group included 18 (3%) adult rheumatological patients with IA, a control group included 610 (87%) adult hematological patients. Rheumatological patients were older, the average age was 59 years (21–75) vs 45 years (18–79), p = 0.005, and among them there were more women – 56% vs 42%, p = 0.01.Results:In rheumatological patients with IA, underlying diseases were ANCA-associated vasculitis (28%), granulomatosis with polyangiitis (22%), periarteritis (11%), systemic lupus erythematosus (22%), rheumatic heart disease (11%) and ankylosing spondylitis (6%). In the control group, underlying diseases were acute leukemia (45%), lymphomas (34%), chronic leukemia (9%), multiple myeloma (7%), myelodysplastic syndrome (3%), and other hematological diseases (2%).The main risk factors for IA development in rheumatological patients were: systemic steroids use (89% vs 69%), prolonged lymphocytopenia (76% vs 65%, median - 14 vs 12 days), treatment in ICU (44% vs 18%, p = 0.01), acute or chronic renal failure (39% vs 1%, p = 0.0008) and immunosuppressive therapy (28% vs 25%). Severe neutropenia was noted significantly less frequently (18% vs 83%, p = 0.0001). Additional risk factors were decompensated diabetes mellitus (17% vs 2%, p = 0.004), previous surgery (17% vs 1%, p = 0.001) and organ transplantation (6% vs 0%). In rheumatological patients, lung (83% vs 98%, p = 0.0001) and ≥2 organs (6% vs 8%) involvement were less common. Heart (11% vs 0%), sinuses (6% vs 5%) and central nervous system (6% vs 4%) involvement more often developed. In rheumatological patients, respiratory failure (61 vs 37%, p = 0.03), hemoptysis (28% vs 7%, p = 0.0001) and chest pain (17% vs 7%, p = 0, 04) were noted more often, less often - fever ≥380С (67% vs 85%, p = 0.01) and cough (61% vs 70%). CT signs of lung damage were similar in both groups, but rheumatologic patients were more likely to show an «air crescent» sign and / or destruction cavity (44% vs 10%, p = 0.0001). In rheumatologic patients, IA was more often confirmed by isolation ofAspergillusspp. from BAL (80% vs 45%, p = 0.005) and by histological examination (22% vs 7%, p = 0.01). The main pathogens wereA. fumigatus(50% vs 43%),A. niger(29% vs 32%), andA. flavus(14% vs 17%).Rheumatological patients were less likely to receive antifungal therapy 89% vs 99%, p = 0,0003. The main drug in both groups was voriconazole. The overall 12-week survival did not significantly differ between groups, but was lower in rheumatological patients with IA (69% vs 81%).Conclusion:In rheumatological patients, invasive aspergillosis more often developed at an older age, mainly in women. The main background diseases were ANCA-associated vasculitis, granulomatosis with polyangiitis, and systemic lupus erythematosus. Typical risk factors were steroids and immunosuppressants use, prolonged lymphocytopenia, ICU stay, and renal failure. The main causative agents wereA. fumigatus,A. niger, andA. flavus. The main localization of infection were lungs. Respiratory failure, hemoptysis and heart involvement were typical. The overall 12-week survival of rheumatological patients with invasive aspergillosis was 69%.Disclosure of Interests:None declared

scholarly journals Pneumocystis jirovecii Pneumonia in Patients with Rheumatic Diseases: Risk Assessment and Prophylaxis

2022 ◽  
pp. 1-7
Author(s):  
Matthew Shing Him Lee ◽  
Shirley Chiu Wai Chan
Keyword(s):  
Risk Factors ◽  
Risk Assessment ◽  
Rheumatic Diseases ◽  
Immunosuppressive Agents ◽  
Pneumocystis Jirovecii ◽  
Pneumocystis Jirovecii Pneumonia ◽  
International Guideline ◽  
Related Factors ◽  
Factors Associated ◽  
Disease Specific

Pneumocystis jirovecii pneumonia (PJP) is an uncommon opportunistic infection in patients with rheumatic diseases with high mortality. Unlike other non-HIV conditions, international guideline for PJP prophylaxis in rheumatic diseases is currently lacking. Recent evidence regarding the risk of PJP and effectiveness of prophylaxis has been accumulating. This Review provides an update on the information about risk factors associated with PJP in patients with rheumatic diseases based on rheumatic diagnoses, use of immunosuppressive agents and other disease-related factors. The second part of the article summarizes evidence regarding the effectiveness of PJP prophylaxis by considering both disease-related and therapy-related factors. Finally, the Review outlined the currently available disease-specific recommendations and local guidelines, and appreciate the factors that influence physicians’ decision.

scholarly journals Early-onset invasive aspergillosis and other fungal infections in patients treated with ibrutinib

Blood ◽  
2018 ◽  
Vol 131 (17) ◽  
pp. 1955-1959 ◽  
Author(s):  
David Ghez ◽  
Anne Calleja ◽  
Caroline Protin ◽  
Marine Baron ◽  
Marie-Pierre Ledoux ◽  
...  
Keyword(s):  
Risk Factors ◽  
Invasive Aspergillosis ◽  
Early Onset ◽  
Fungal Infections ◽  
Invasive Fungal Infections ◽  
Key Points

Key Points Ibrutinib may be associated with invasive fungal infections especially IA. Most infections usually occur during the first months of treatment, often in patients with other risk factors for fungal infections.

Profile of common inflammatory markers in treatment-naïve patients with systemic rheumatic diseases

2020 ◽  
Author(s):  
Min Jung Kim ◽  
Eun Bong Lee ◽  
Yeong Wook Song ◽  
Jin Kyun Park
Keyword(s):  
Rheumatic Diseases ◽  
Lupus Erythematosus ◽  
Inflammatory Markers ◽  
Acute Phase Proteins ◽  
Acute Infection ◽  
Inflammatory Myopathy ◽  
University Hospital ◽  
Treatment Naïve ◽  
Systemic Rheumatic Diseases ◽  
Wbc Count

Abstract Background The host inflammatory response against infection is characterized by leukocytosis, and the release of cytokines and acute phase proteins. However, routine inflammatory markers are not always elevated in systemic rheumatic diseases (SRD). Here, we aimed to systematically evaluate and compare the clinical implications of common inflammatory markers in systemic rheumatic diseases (SRDs). Methods We investigated the profiles of erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and white blood cell (WBC) count in treatment-naïve patients with SRDs, osteoarthritis and pneumonia diagnosed at Seoul National University Hospital during 2004-2016. SRDs included rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), ankylosing spondylitis (AS), systemic sclerosis (SSc), idiopathic inflammatory myopathy (IIM) and adult onset of Still disease (AOSD). Associations between inflammatory markers were evaluated using Pearson’s correlation and regression analysis. Differences between correlations were compared using Steiger’s z-test. Receiver operating characteristic (ROC) curve analysis was performed to examine the predictive value of inflammatory markers for SRD diagnosis. Results We identified 1191 patients with SRDs, osteoarthritis and pneumonia. Leukocytosis was present in <15% SRD patients. There was marked variability in ESR and CRP levels among different SRDs. The highest mean CRP levels (mean ± SD, mg/dL) were observed in those with AOSD (11.3±7.9), followed by RA (2.0±3.3), IIM (1.8±3.5), SLE (1.5±3.1), SSc (0.6±1.3) and AS (0.08±0.1). Mean ESR (mm/hr) was also highest in AOSD (71.2±31.0), followed by SLE (47.3±34.2), RA (45.5±30.6), IIM (40.8±24.8) and SSc (27.8±26.0). All SRDs showed significant positive correlations between ESR and CRP: greatest in RA (r=0.53, p<0.001) and weakest in SLE (r=0.20, p=0.03). WBC correlated weakly with CRP but not with ESR in most SRDs. While the AUC for WBC count (0.54-0.68) was less than that of ESR or CRP, the AUC for ESR and CRP (0.69-0.86) were similar in SRD. The optimal cuff-off values for inflammatory markers predicting SRD were within or slightly above the normal limit. Conclusions Unlike acute infection, ESR, CRP and WBC count are not always elevated in treatment-naïve patients with SRD. Thus, common inflammatory markers have limited value for diagnosis and assessment of disease activity of SRD.

scholarly journals Innate Lung Defense during Invasive Aspergillosis: New Mechanisms

2017 ◽  
Vol 9 (3) ◽  
pp. 271-280 ◽  
Author(s):  
Jaleesa M. Garth ◽  
Chad Steele
Keyword(s):  
Invasive Aspergillosis ◽  
Defense Mechanisms ◽  
Fungal Infections ◽  
Immunosuppressive Agents ◽  
Innate Immune ◽  
Pulmonary System ◽  
Continued Use ◽  
Primary Risk Factor ◽  
Primary Agent ◽  
Lung Defense

Invasive aspergillosis (IA) is one of the most difficult to treat and, consequently, one of the most lethal fungal infections known to man. Continued use of immunosuppressive agents during chemotherapy and organ transplantation often leads to the development of neutropenia, the primary risk factor for IA. However, IA is also becoming more appreciated in chronic diseases associated with corticosteroid therapy. The innate immune response to Aspergillus fumigatus, the primary agent in IA, plays a pivotal role in the recognition and elimination of organisms from the pulmonary system. This review highlights recent findings about innate host defense mechanisms, including novel aspects of innate cellular immunity and pathogen recognition, and the inflammatory mediators that control infection with A. fumigatus.

Invasive aspergillosis: a severe infection in juvenile systemic lupus erythematosus patients

Lupus ◽  
2012 ◽  
Vol 21 (9) ◽  
pp. 1011-1016 ◽  
Author(s):  
MF Silva ◽  
AS Ribeiro ◽  
FJ Fiorot ◽  
NE Aikawa ◽  
AP Lotito ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Invasive Aspergillosis ◽  
Lupus Erythematosus ◽  
Activity Index ◽  
Large Population ◽  
Immunosuppressive Agents ◽  
Immunosuppressive Drugs ◽  
Systemic Lupus ◽  
Juvenile Systemic Lupus Erythematosus ◽  
Systemic Involvement

Infections are an important cause of morbidity and mortality in juvenile systemic lupus erythematosus (JSLE). Among them, invasive aspergillosis (IA), which is usually related to immunosuppressed patients, has been rarely reported in JSLE. From 1983 to 2011, 5604 patients were followed at our institution and 283 (5%) met the American College of Rheumatology (ACR) classification criteria for SLE. Six (2.1%) of our JSLE patients had IA. One of them was previously reported and five will be described herein. Four of them were female. The median age at JSLE diagnosis was 12 years (8–16) and the median interval between diagnosis of JSLE and IA was 6 months (1–38). All had pulmonary involvement and three of them had systemic involvement. The median Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) was 19 (7–22). Diagnosis of IA was performed by isolation of Aspergillus spp., two in bronchoalveolar lavage culture and by way of autopsy in the others. All of them were treated with corticosteroids and/or immunosuppressive drugs at IA diagnosis (azathioprine and/or intravenous cyclophosphamide). They all required treatment in the pediatric intensive care unit with mechanical ventilation and antifungal therapy (fluconazole, amphotericin B, itraconazole and/or voriconazole); nonetheless, none of them survived. In conclusion, this was the first report that evaluated the prevalence of IA in a large population of JSLE patients from a tertiary pediatric hospital, and clearly showed the severity of the outcome, especially in patients with active disease and treated with immunosuppressive agents. This study reinforces the importance of early diagnosis and treatment with certain antifungals, especially in critically ill patients.

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