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Cureus Jun 2024X-linked inhibitor of apoptosis (XIAP) deficiency is a rare primary immunodeficiency with a broad spectrum of clinical manifestations, including susceptibility to...
X-linked Inhibitor of Apoptosis (XIAP) Deficiency Complicated by Hemophagocytic Lymphohistiocytosis on Immunotherapy Leading to Acute Respiratory Distress Syndrome and Multiorgan Failure Secondary to Opportunistic Infections.
X-linked inhibitor of apoptosis (XIAP) deficiency is a rare primary immunodeficiency with a broad spectrum of clinical manifestations, including susceptibility to hemophagocytic lymphohistiocytosis (HLH), inflammatory bowel disease (IBD), hypogammaglobulinemia, and severe infections. We present a case of a 39-year-old male with a past medical history of XIAP deficiency complicated by HLH, Crohn's disease, and hypogammaglobulinemia, who developed acute respiratory distress syndrome (ARDS) due to Pneumocystis jiroveci pneumonia (PJP) and concurrent multiorgan failure due to disseminated Mycobacterium avium intracellulare (MAI) infection. This case highlights the challenges in managing XIAP deficiency, emphasizing the importance of early recognition, and the need for further research to improve outcomes in this population.
PubMed: 38912075
DOI: 10.7759/cureus.62703 -
Annales D'endocrinologie Jun 2024
PubMed: 38902161
DOI: 10.1016/j.ando.2024.05.001 -
Cureus May 2024pneumonia (PCP) is a life-threatening condition found in immunocompromised individuals, especially in human immunodeficiency virus (HIV) positive patients. Here, we...
pneumonia (PCP) is a life-threatening condition found in immunocompromised individuals, especially in human immunodeficiency virus (HIV) positive patients. Here, we report a case of PCP in a presumably immunocompetent 25-year-old male patient who presented with a one-month history of chest pain, dyspnea, and a nonproductive cough with recent development of night sweats. The patient recently immigrated to the United States without any known medical or family history. A chest radiograph revealed moderate pneumothorax for which a chest tube was placed. A chest computed tomography (CT) scan revealed diffuse lung disease with multiple thin- and thick-walled cystic lesions on a background of diffuse ground-glass opacities. Based on these radiologic findings and subsequent positive HIV serology, there was a high suspicion of PCP. Bronchoalveolar lavage was performed, and PCR for was positive. Appropriate treatment was initiated, and the patient recovered well. Through this report, we aim to highlight the importance of recognizing the various clinical and radiologic findings of PCP even in patients with no overt risk factors. Prompt and targeted treatment could mitigate morbidity and mortality associated with this opportunistic pathogen.
PubMed: 38899257
DOI: 10.7759/cureus.60697 -
Journal of Clinical Immunology Jun 2024Patients with chromosome 18q deletion syndrome generally experience hypogammaglobulinemia. Herein, we describe two patients with chromosome 18q deletion syndrome who...
Patients with chromosome 18q deletion syndrome generally experience hypogammaglobulinemia. Herein, we describe two patients with chromosome 18q deletion syndrome who presented with late-onset combined immune deficiency (LOCID), which has not been previously reported. Patient 1 was a 29-year-old male with 18q deletion syndrome, who was being managed for severe motor and intellectual disabilities at the Yamabiko Medical Welfare Center for 26 years. Although the patient had few infections, he developed Pneumocystis pneumonia at the age of 28. Patient 2, a 48-year-old female with intellectual disability and congenital malformations, was referred to Tokyo Medical and Dental University Hospital with abnormal bilateral lung shadows detected on her chest radiography. Computed tomography showed multiple lymphadenopathies and pneumonia. A lymph node biopsy of the inguinal region revealed granulomatous lymphadenitis, and a chromosomal examination revealed 18q deletion. Array-based genomic hybridization analysis revealed deletion at 18q21.32-q22.3 for patient 1 and at 18q21.33-qter for patient 2. Immune status work-up of the two patients revealed panhypogammaglobulinemia, decreased number of memory B cells and naïve CD4 and/or CD8 cells, reduced response on the carboxyfluorescein diacetate succinimidyl ester T-cell division test, and low levels of T-cell receptor recombination excision circles and Ig κ-deleting recombination excision circles. Consequently, both patients were diagnosed with LOCID. Although patients with 18q deletion syndrome generally experience humoral immunodeficiency, the disease can be further complicated by cell-mediated immunodeficiency, causing combined immunodeficiency. Therefore, patients with 18q deletion syndrome should be regularly tested for cellular/humoral immunocompetence.
Topics: Humans; Chromosome Deletion; Male; Female; Chromosomes, Human, Pair 18; Chromosome Disorders; Adult; Middle Aged; Age of Onset; Severe Combined Immunodeficiency; Intellectual Disability; Immunologic Deficiency Syndromes
PubMed: 38896123
DOI: 10.1007/s10875-024-01751-4 -
BMC Pulmonary Medicine Jun 2024Persistent inflammatory damage and suppressed immune function play a crucial role in the pathogenesis and progression of the pneumocystis jirovecii pneumonia (PjP).... (Observational Study)
Observational Study
Persistent inflammatory damage and suppressed immune function play a crucial role in the pathogenesis and progression of the pneumocystis jirovecii pneumonia (PjP). Therefore, we aimed to investigate the correlation between the combined immune and inflammatory indicator: the neutrophil-to-lymphocyte ratio (NLR) and prognosis of non-human immunodeficiency virus (non-HIV) PjP.In the retrospective analysis conducted in ICUs at Beijing Chao-Yang Hospital, we examined data from 157 patients diagnosed with non-HIV PjP. Our findings reveal a concerning hospital mortality rate of 43.3%, with the 28-day mortality rate reaching 47.8%.Through multivariable logistic and Cox regression analyses, we established a significant association between elevated NLR levels and hospital mortality (adjusted odd ratio, 1.025; 95% CI, 1.008-1.043; p = 0.004) or 28-day mortality (adjusted hazard ratio, 1.026; 95% CI, 1.008-1.045; p = 0.005). Specifically, patients with an NLR exceeding 20.3 demonstrated markedly lower overall survival rates, underscoring the biomarker's predictive value for both hospital and 28-day mortality.In conclusion, non-HIV PjP patients in the ICU still have a high rate of mortality and a poor short-term prognosis after discharge. A high level of NLR was associated with an increased risk of hospital mortality and 28-day mortality.
Topics: Humans; Pneumonia, Pneumocystis; Retrospective Studies; Male; Female; Middle Aged; Neutrophils; Prognosis; Aged; Hospital Mortality; Pneumocystis carinii; Lymphocytes; China; Logistic Models; Intensive Care Units; Biomarkers; Proportional Hazards Models; Adult
PubMed: 38890590
DOI: 10.1186/s12890-024-03093-8 -
Open Forum Infectious Diseases Jun 2024Prior reports have suggested a possible increase in the frequency of invasive fungal infections (IFIs) with use of a Bruton tyrosine kinase inhibitor (BTKi) for...
Risk of Invasive Fungal Infections in Patients With Chronic Lymphocytic Leukemia Treated With Bruton Tyrosine Kinase Inhibitors: A Case-Control Propensity Score-Matched Analysis.
BACKGROUND
Prior reports have suggested a possible increase in the frequency of invasive fungal infections (IFIs) with use of a Bruton tyrosine kinase inhibitor (BTKi) for treatment of chronic lymphoid malignancies such as chronic lymphocytic leukemia (CLL), but precise estimates are lacking. We aim to characterize the prevalence of IFIs among patients with CLL, for whom a BTKi is now the first-line recommended therapy.
METHODS
We queried TriNetX, a global research network database, to identify adult patients with CLL using the code (C91.1) and laboratory results. We performed a case-control propensity score-matched analysis to determine IFIs events by BTKi use. We adjusted for age, sex, ethnicity, and clinical risk factors associated with an increased risk of IFIs.
RESULTS
Among 5358 matched patients with CLL, we found an incidence of 4.6% of IFIs in patients on a BTKi versus 3.5% among patients not on a BTKi at 5 years. Approximately 1% of patients with CLL developed an IFI while on a BTKi within this period. Our adjusted IFI event analysis found an elevated rate of pneumonia (PJP) (0.5% vs 0.3%, = .02) and invasive candidiasis (3.5% vs 2.7%, = .012) with the use of a BTKi. The number needed to harm for patients taking a BTKi was 120 and 358 for invasive candidiasis and PJP, respectively.
CONCLUSIONS
We found an adjusted elevated rate of PJP and invasive candidiasis with BTKi use. The rates are, however, low with a high number needed to harm. Additional studies stratifying other IFIs with specific BTKis are required to identify at-risk patients and preventive, cost-effective interventions.
PubMed: 38887474
DOI: 10.1093/ofid/ofae115 -
Current HIV Research Jun 2024Vitamin D deficiency and/or insufficiency (hypovitaminosis D) has been associated with several disorders including autoimmune diseases, like type 1 diabetes mellitus;...
BACKGROUND
Vitamin D deficiency and/or insufficiency (hypovitaminosis D) has been associated with several disorders including autoimmune diseases, like type 1 diabetes mellitus; cardiovascular diseases; neoplasms; obesity; insulin resistance, and type 2 diabetes mellitus. This problem is common in southern European countries, especially in elderly and institutionalized persons. In HIV-infected individuals, hypovitaminosis D has been correlated with various complications like tuberculosis, hyperparathyroidism, bone mass loss, premature atherosclerosis, and systemic arterial hypertension, deterioration of immune function, progression of the disease and overall mortality.
OBJECTIVE
The objective of this study was to examine the prevalence and causes of hypovitaminosis D in a cohort of Greek HIV-infected patients, the factors, and possible complications associated with it.
METHODS
All patients attending our HIV unit for a period of 5 months were included in this study. Vitamin D status, medical anamnes, and laboratory tests were obtained at baseline; patients were followed for 3 years and HIV-related complications were noted. No patient received vitamin D supplementation during the follow-up period.
RESULTS
Hypovitaminosis D was common, with 83.7% of the patients showing levels below 30ng/dl and 55.4% below 20ng/dl. After multivariable analysis, age and duration of treatment were the only significant factors for low vitamin D levels. During follow-up, 26 patients exhibited a total of 34 HIV-related complications, the most common being pneumonocystis jiroveci pneumonia (PCP). Hypovitaminosis D showed a positive correlation with overall complications, PCP as well as wasting syndrome.
CONCLUSION
Overall, our study shows that hypovitaminosis D is common in HIV-infected individuals and should probably be treated as soon as possible to protect these patients from serious HIVrelated complications like PCP or wasting syndrome.
PubMed: 38874038
DOI: 10.2174/011570162X302844240605104855 -
Current Research in Microbial Sciences 2024Ibrexafungerp (IBX) is a new antifungal drug that recently entered the antifungal landscape. It disrupts fungal cell wall synthesis by non-competitive inhibition of the... (Review)
Review
Ibrexafungerp (IBX) is a new antifungal drug that recently entered the antifungal landscape. It disrupts fungal cell wall synthesis by non-competitive inhibition of the β-(1,3)-D-glucan (BDG) synthase enzyme. It has demonstrated activity against a range of pathogens including and spp., as well as retaining its activity against azole-resistant and echinocandin-resistant strains. It also exhibits anti-biofilm properties. Pharmacokinetic (PK) studies revealed favorable bioavailability, high protein binding, and extensive tissue distribution with a low potential for CYP-mediated drug interactions. It is characterized by the same mechanism of action of echinocandins with limited cross-resistance with other antifungal agents. Resistance to this drug can arise from mutations in the genes, primarily mutations in . In vivo, IBX was found to be effective in murine models of invasive candidiasis (IC) and invasive pulmonary aspergillosis (IPA). It also showed promising results in preventing and treating infections. Clinical trials showed that IBX was effective and non-inferior to fluconazole in treating vulvovaginal candidiasis (VVC), including complicated cases, as well as in preventing its recurrence. These trials positioned it as a Food and Drug Administration (FDA)-approved option for the treatment and prophylaxis of VVC. Trials showed comparable responses to standard-of-care in IC, with favorable preliminary results in infections in terms of efficacy and tolerability as well as in refractory cases of IC. Mild adverse reactions have been reported including gastrointestinal symptoms. Overall, IBX represents a significant addition to the antifungal armamentarium, with its unique action, spectrum of activity, and encouraging clinical trial results warranting further investigation.
PubMed: 38873590
DOI: 10.1016/j.crmicr.2024.100245 -
Infection and Drug Resistance 2024The administration of trimethoprim-sulfamethoxazole (TMP-SMX) for the prophylaxis of Pneumocystis jirovecii pneumonia (PJP) has proven to be highly efficacious in...
Clinical Characteristics and Epidemiological Analysis of Pneumocystis Jirovecii Pneumonia Infection in Kidney Transplant Patients with Trimethoprim-Sulfamethoxazole Dose Reduction Prophylaxis Strategy.
BACKGROUND
The administration of trimethoprim-sulfamethoxazole (TMP-SMX) for the prophylaxis of Pneumocystis jirovecii pneumonia (PJP) has proven to be highly efficacious in individuals who have undergone kidney transplantation. Nevertheless, the potential for severe adverse reactions associated with this treatment cannot be overlooked, and the determination of an optimal dosage regimen continues to be a matter of investigation. The current study evaluated the effectiveness of low-dose TMP-SMX for PJP prophylaxis in kidney transplant patients and conducted an analysis of the clinical characteristics and epidemiological trends in patients with PJP infection.
METHODS
This retrospective analysis studied electronic medical records of 1763 kidney transplant recipients from 2017 to 2020. These patients were initially prescribed a daily half-strength TMP-SMX (40 mg/200 mg), and the efficacy of this regimen was assessed during a follow-up period of 3-51 months.
RESULTS
Under our PJP prevention and adjustment strategy, 24 patients were infected with PJP. The overall morbidity of PJP infection in our study was 1.36%, corroborates with findings from previously published studies. Among these 24 patients, up to 87.5% had their dosage adjusted due to increased creatinine or other adverse reactions, the most frequent dose was daily quarter-strength TMP-SMX (20 mg/100 mg). TMP-SMX prophylaxis successfully postponed and distributed the onset of PJP, with the mean duration from transplantation to the occurrence of PJP being 13.50±7.11 months.
CONCLUSION
Daily administration of half-strength TMP-SMX can effectively prevent PJP, and prolonging prophylaxis with this medication may potentially reduce the incidence of infection.
PubMed: 38868399
DOI: 10.2147/IDR.S461206 -
Open Forum Infectious Diseases Jun 2024An early diagnosis and treatment of invasive fungal disease (IFD) is associated with improved outcome, but the moderate sensitivity of noninvasive diagnostic tests makes...
BACKGROUND
An early diagnosis and treatment of invasive fungal disease (IFD) is associated with improved outcome, but the moderate sensitivity of noninvasive diagnostic tests makes this challenging. Invasive diagnostic procedures such as bronchoalveolar lavage (BAL) have a higher yield but are not without risk. The detection and sequencing of microbial cell-free DNA (mcfDNA) may facilitate a noninvasive diagnosis.
MATERIALS
In a prospective observational study, we collected plasma in the 120 hours preceding or following a BAL in patients with hematological malignancies suspected for a pulmonary IFD. The EORTC/MSGERC2020 criteria were used for IFD classification. Sequencing was performed by Karius (Redwood City, CA) using their Karius Test (KT) on plasma and a "research use only test" on BAL fluid if available. Cases with a probable/proven IFD were identified based on standard diagnostic tests on serum and BAL (microscopy, polymerase chain reaction, galactomannan, culture) and used to calculate the sensitivity, specificity, and additional diagnostic value of the KT.
RESULTS
Of 106 patients enrolled, 39 (37%) had a proven/probable invasive aspergillosis, 7 (7%) a non- IFD, and 4 (4%) a mixed IFD. The KT detected fungal mcfDNA in 29 (28%) patients. Compared with usual diagnostic tests, the sensitivity and specificity were 44.0% (95% confidence interval [CI], 31.2-57.7) and 96.6% (95% CI, 88.5%-99.1%). Sensitivity of the KT was higher in non- IFD (:2/3, : 3/5). On BAL, the sensitivity was 72.2% (95% CI, 62.1-96.3), and specificity 83.3% (95% CI, 49.1-87.5).
CONCLUSIONS
Sequencing of mcfDNA may facilitate a noninvasive diagnosis of IFD in particular non- IFD. However, on plasma and similar to currently available diagnostics, it cannot be used as a "rule-out" test.
PubMed: 38868302
DOI: 10.1093/ofid/ofae252