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J Assoc Physicians India. 2025 Jul;73(7S):17-19. doi: 10.59556/japi.73.0978.

ABSTRACT

Over the past few years, there has been a significant rise in the prevalence of human fungal infections worldwide, largely due to factors such as the acquired immunodeficiency syndrome (AIDS) pandemic, widespread use of antibacterial agents, and the utilization of chemotherapeutic agents for treating neoplastic diseases. Histoplasmosis, attributed to the dimorphic fungus Histoplasma capsulatum, is one such opportunistic fungal infection. It is endemic to regions along the “Ohio” and “Mississippi” river valleys and is frequently located in soil tainted by bat or bird feces. Cases occurring outside these endemic areas are often due to imported diseases. Histoplasmosis is not considered endemic in India, but regions with high prevalence have been reported in the Gangetic plain, particularly in West Bengal and Uttar Pradesh. The prevalence of histoplasmosis in India, as determined by histoplasmin skin sensitivity testing, ranges from 0 to 12.3%. Infection typically occurs through inhalation of spores, with the majority of cases being asymptomatic or presenting with minimal symptoms in over 99% of patients. Symptomatic cases usually manifest as acute pulmonary histoplasmosis, which is a self-limiting illness resembling atypical pneumonia. However, immunocompromised individuals, particularly those with impaired T-cell immunity, may fail to elicit appropriate immunological responses, leading to the development of disseminated histoplasmosis. This form of infection can manifest with symptoms such as anorexia, pancytopenia, fever, weight loss, hepatosplenomegaly, as well as mucosal ulceration. Histoplasmosis resulting in isolated lymphadenopathy is uncommon, especially in India, where tuberculosis constitutes the primary etiology in the majority of instances. Diverse and ambiguous symptoms of histoplasmosis often lead to misdiagnosis or underreporting of infections. Thus, it is essential to include histoplasmosis in the list of potential causes for cervical lymphadenopathy, especially among immunocompromised individuals. Early medical intervention is essential to prevent dissemination of the disease. The presentation of histoplasmosis with cervical lymphadenopathy is uncommon, and we present a case of such occurrence here.

PMID:40836742 | DOI:10.59556/japi.73.0978

Balkan Med J. 2025 Aug 20. doi: 10.4274/balkanmedj.galenos.2025.2025-6-247. Online ahead of print.

ABSTRACT

BACKGROUND: Childhood bronchiectasis (BE) is a chronic lung condition that remains under recognized, marked by irreversible widening of the bronchi, frequent respiratory infections, a persistent wet cough, and progressive lung damage, often leading to significant health burdens.

AIMS: Evaluate children with cystic fibrosis (CF) and non-CF BE and to examine the association between clinical presentation and radiological severity of BE using the Bhalla scoring system.

STUDY DESIGN: Retrospective, single-center observational study.

METHODS: Children aged 0-18 years with a CT-confirmed diagnosis of BE were enrolled. Data on demographics, clinical characteristics, and imaging results were collected retrospectively from medical records. The Bhalla score was used to assess BE severity. Patients were categorized into CF-related and non-CF BE groups. The two groups were compared with respect to clinical features, growth z-scores, hospitalization frequency, and pulmonary function test outcomes.

RESULTS: A total of 157 patients were analyzed. Among them, CF accounted for 23.6% of cases, and while the leading causes in the non-CF group were post-infectious BE (28%), immunodeficiency (19.8%), and primary ciliary dyskinesia (12.8%). The CF group presented at an earlier age, had a longer follow-up period, and experienced more frequent hospitalizations (p < 0.001). In the CF group, weight, height, and body mass index z-scores significantly improved from the initial to the final assessment (p = 0.010, p = 0.006, and p = 0.026, respectively), whereas no such improvement was observed in the non-CF group. Severe Bhalla scores were more frequently observed in the CF group (p < 0.001). Among CF patients, Bhalla scores showed a strong correlation with forced expiratory volume in one second (FEV₁) in univariate analysis (r = 0.846, p < 0.001), though this was not significant in multivariable analysis (p = 0.434). In the non-CF group, there was no correlation between Bhalla scores and final FEV₁ values (p = 0.148, r = 0.212).

CONCLUSION: The results underscore distinct clinical trajectories between CF and non-CF BE in children. Improvements in CF patients suggest the effectiveness of structured clinical management, whereas inconsistent outcomes in non-CF patients point to the need for standardized follow-up protocols. While the Bhalla score may indicate the extent of structural lung disease in CF, it does not independently predict lung function, and therefore should be used as a supplementary, not solitary, measure of disease severity.

PMID:40832796 | DOI:10.4274/balkanmedj.galenos.2025.2025-6-247

medRxiv [Preprint]. 2025 Aug 12:2025.08.08.25333317. doi: 10.1101/2025.08.08.25333317.

ABSTRACT

PURPOSE: Copy number variants (CNVs) are a major contributor to rare genetic diseases, but their detection and interpretation from short-read genome sequencing (srGS) data remain challenging, especially at scale. Large amounts of existing srGS data remain under-analyzed for clinically relevant CNVs.

METHODS: During a collaborative Hackathon, we developed and applied scalable CNV analysis workflows to srGS data from three unsolved, exome-negative, rare disease cohorts: Primary Immunodeficiency (N = 39), Turkish developmental disorders (N = 31), and data from the Genomics Research to Elucidate the Genetics of Rare diseases (GREGoR) (N = 1437). We employed Parliament2 for structural variant (SV) calling, Mosdepth and SLMSuite for read-depth-based quality control and CNV detection, and R Shiny-based visualization tools. We also constructed an SV/CNV variant database with population frequency and pathogenicity annotations, applied DBSCAN clustering for internal allele frequency estimation, and used a 3-way annotation strategy to aid interpretation.

RESULTS: Our pipelines identified high-confidence CNVs and streamlined interpretation across cohorts. Within 2 days, the Hackathon yielded 39 candidate pathogenic SVs. The tools and workflows enabled rapid filtering, prioritization, and visualization of clinically relevant variants.

CONCLUSION: This community-driven effort demonstrates the feasibility and utility of scalable CNV analysis for accelerating diagnosis and discovery in rare disease cohorts using srGS data.

PMID:40832433 | PMC:PMC12363759 | DOI:10.1101/2025.08.08.25333317

Patient Prefer Adherence. 2025 Aug 13;19:2459-2491. doi: 10.2147/PPA.S515565. eCollection 2025.

ABSTRACT

PURPOSE: Subcutaneous (SC) administration is largely established as the preferred route to deliver biotherapeutics. Although the majority of approved SC products are limited to dose volumes ≤2.25 mL, there has been increasing industry focus on large-volume SC (LVSC) development. To date, however, there are few LVSC biotherapeutics available for self-administration, and subcutaneous immunoglobulin (SCIg) remains the most established example. As a result, there is limited published literature on real-world practices with LVSC therapies to inform user needs and preferences for delivery device design attributes.

PATIENTS AND METHODS: This was a remote ethnography study of patients self-administering SCIg at home for treatment of primary immunodeficiency diseases (PIDD). Participants passively video recorded their preparation and infusion processes, took photos, and provided open responses to illustrate their overall experiences with their disease, infusions, and delivery devices. Qualitative data were compiled, analyzed, and grouped into themes and subthemes that represented participant responses and sentiments.

RESULTS: A total of 11 patients completed the remote study, all of whom were diagnosed with PIDD. Enrolled participants were currently infusing SCIg with one of five delivery devices and most also had previous experience with another delivery device. Emerging themes included universal preference for SC administration and pain points associated with managing medication/supply orders, storing medications/supplies, troubleshooting device issues, performing burdensome medication preparations, priming tubing/needles, inserting/securing needles, programming devices, adapting to device volume constraints, and loading reservoirs or tubing into delivery devices.

CONCLUSION: Although patients prefer LVSC administration at home compared to the alternatives, the current SCIg use process presents a variety of challenges. While not all of these factors will apply to every LVSC scenario, these insights, along with their corresponding implications for device design, provide a framework to inform user needs for LVSC self-administration, anticipate obstacles during development of new LVSC therapies, and improve existing delivery devices.

PMID:40827209 | PMC:PMC12358116 | DOI:10.2147/PPA.S515565

Pediatr Allergy Immunol Pulmonol. 2025 Aug 18. doi: 10.1177/2151321X251368265. Online ahead of print.

ABSTRACT

Patients with pathogenic variants of lipopolysaccharide-responsive beige-like anchor protein (LRBA) are known to present with autoimmune diseases, inflammatory bowel disease, lymphoproliferative disorders, allergies, immunodeficiency, and malignancies. This condition, characterized by widespread infections that impact multiple systems, has various radiological findings reported in the literature. These include computed tomography (CT) findings indicating lung involvement and magnetic resonance imaging (MRI) findings showing neurological system involvement. However, F-18 fluorodeoxyglucose positron emission tomography-CT (FDG PET-CT) imaging findings in LRBA deficiency have not yet been described in the literature. This report presents multiple organ involvements detected by F-18 FDG PET-CT in a case with an LRBA gene variant. FDG PET-CT findings for diagnostic and primary focus evaluation were reviewed in a 17-year-old male patient with a pathogenic LRBA variant, prompted by multiple hypoechoic nodular appearances identified on abdominal ultrasonography. In this patient, who carried a pathogenic LRBA variant (c.3396-3397delAC, p.D975Yfs*15) and was treated with abatacept for liver involvement, FDG PET-CT revealed a wide range of system involvements. These included the lungs, liver, intestines, bone, bone marrow, and lymph nodes, as well as multiple joints and tendons. In immunodeficiency diseases with such extensive multisystem involvement, whole-body imaging techniques like F-18 FDG PET-CT can serve as valuable tools for physicians to comprehensively assess the disease and formulate effective treatment strategies.

PMID:40824749 | DOI:10.1177/2151321X251368265

Front Allergy. 2025 Aug 1;6:1639718. doi: 10.3389/falgy.2025.1639718. eCollection 2025.

ABSTRACT

Health disparities in allergic and immunologic conditions are shaped by unequal exposure to social determinants of health (SDoH), including education, healthcare quality, neighborhood and built environment, social context, and economic stability. This review summarizes recent literature on disparities across asthma, food allergy, eosinophilic esophagitis, atopic dermatitis, allergic rhinitis, chronic rhinosinusitis, drug allergy, and primary immunodeficiency. Marginalized populations-including Black, Latinx, and low-income individuals-experience delayed diagnoses, limited access to specialist care, underuse of evidence-based therapies, and disproportionate exposure to environmental triggers. The manuscript highlights successful interventions including community health worker-led outreach, school-based programs, housing modifications, and policy reforms addressing affordability, housing, and environmental quality. However, recent cuts to federal agency staffing and funding jeopardize continued progress, threatening public health infrastructure that supports equitable care for many diseases. Sustained investment, interdisciplinary collaboration, and policy-driven strategies remain critical to addressing persistent inequities and improving outcomes in historically underserved communities.

PMID:40823368 | PMC:PMC12354566 | DOI:10.3389/falgy.2025.1639718

J Perianesth Nurs. 2025 Aug 14:S1089-9472(25)00341-7. doi: 10.1016/j.jopan.2025.05.180. Online ahead of print.

ABSTRACT

Common variable immunodeficiency (CVID) is one of the most common forms of severe primary immunodeficiency, characterized by a deficiency of immunoglobulin G (IgG) and impaired antibody responses, which increase susceptibility to infections. Anesthetic management of patients with CVID and end-stage liver disease is extremely challenging for anesthesiologists. We report the successful anesthesia management of a 46-year-old female patient with end-stage liver disease, diagnosed with CVID at age 26, by applying timely intravenous immunoglobulin and prophylactic antibiotic therapy for laparoscopic cholecystectomy and hernia repair surgery. Increasing knowledge and awareness of perioperative staff, along with a comprehensive preoperative evaluation, is important in caring for patients with CVID, contributing significantly to preoperative preparation, intraoperative monitoring, and postoperative recovery, as well as ensuring patient safety and optimizing outcomes.

PMID:40815253 | DOI:10.1016/j.jopan.2025.05.180

J Family Med Prim Care. 2025 Jul;14(7):2643-2652. doi: 10.4103/jfmpc.jfmpc_1582_24. Epub 2025 Jul 21.

ABSTRACT

Invasive fungal infections, being opportunistic, lead to severe disease in immunocompromised hosts with an increase in morbidity and mortality. The most common causative agents include Candida, Mucorales, Aspergillus, Cryptococcus, and Pneumocystis species. The common risk factors associated with invasive fungal infections are uncontrolled diabetes mellitus leading to hyperglycemia, neutropenia, immunosuppressive treatment like corticosteroids, and primary and secondary immunodeficiency disorders, especially acquired immunodeficiency syndrome. Various molecular therapeutic agents used for targeted therapy are also associated with an increase in opportunistic infections as they involve many signaling pathways related to immunity against pathogens. Prompt diagnosis of diseases caused by these invasive fungal infections is necessary because immunosuppression increases the risk of fatality, and treatment should be initiated immediately based on susceptibility and recommendations.

PMID:40814543 | PMC:PMC12349787 | DOI:10.4103/jfmpc.jfmpc_1582_24

Hum Vaccin Immunother. 2025 Dec;21(1):2537482. doi: 10.1080/21645515.2025.2537482. Epub 2025 Aug 14.

ABSTRACT

We report and analyze three cases of disseminated BCG infection in infants after BCG vaccination that occurred between 2022 and 2024 in Chaoyang District, Beijing, which were the only three monitored during the clinical application we conducted. All the patients had primary immunodeficiency disease (PID). Two cases had defects in the JAK3 and TNFRSF13B genes; one case had multiple gene defects in CR2, IFNAR2, TLR2, and exon 13 of DOCK11. Disseminated BCG infection is a rare adverse reaction after BCG vaccination. It occurs almost exclusively in immunodeficient infants or children. Although it rarely occurs, it is necessary to pay more attention to clinical practice because of its serious consequences.

PMID:40811145 | DOI:10.1080/21645515.2025.2537482

J Clin Med. 2025 Jul 29;14(15):5353. doi: 10.3390/jcm14155353.

ABSTRACT

Background/Objectives: Inborn errors of immunity (IEIs) represent a wide spectrum of diseases characterized by a predisposition to recurrent infections, as well as increased susceptibility to autoimmune, atopic, and autoinflammatory diseases and malignancies. The aim of this study was to report the registry-based frequency and describe the clinical characteristics of IEIs among patients in the Republic of Kazakhstan. Methods: We analyzed data from 269 patients belonging to 204 families who were either self-referred or referred by healthcare providers to the University Medical Center of Nazarbayev University with suspected IEIs. All patients resided in various regions across Kazakhstan. Results: A total of 269 diagnosed cases were identified in the national registry. The estimated prevalence was 1.3 per 100,000 population. The gender ratio was nearly equal, with 139 males and 130 females. The median age at diagnosis was 5 years (range: 1 month to 70 years), while the mean age was 11.3 years. The most common diagnosis was humoral immunodeficiency, observed in 120 individuals (44.6%), followed by complement deficiencies in 83 individuals (30.8%). Combined immunodeficiencies with syndromic features were found in 35 patients (13%), and phagocytic cell defects were identified in 12 patients (4.5%). The predominant clinical manifestations included severe recurrent infections and autoimmune cytopenias, while atopic and autoinflammatory symptoms were reported less frequently. Conclusions: These findings contribute to a better understanding of the registry-based distribution and clinical spectrum of IEIs in Kazakhstan and underscore the importance of early diagnosis and targeted care for affected individuals.

PMID:40806973 | DOI:10.3390/jcm14155353