Manish Butte

BMJ Case Rep. 2025 Jul 5;18(7):e263989. doi: 10.1136/bcr-2024-263989.

ABSTRACT

SummaryHereditary angioedema (HAE) is a genetic disorder that causes sudden episodes of swelling, often accompanied by abdominal pain. Affecting roughly 1 in 50 000 people, HAE typically appears in childhood. The condition stems from a deficiency or dysfunction of C1-esterase inhibitor (C1-INH), which triggers uncontrolled inflammation. Diagnosis depends on factors level and function. Treatment focuses on managing acute attacks and preventing future episodes using medications such as C1-INH replacement among other options. In this case, a middle childhood boy experienced severe abdominal pain and vomiting. A detailed family history revealed a pattern of HAE among relatives. Lab results confirmed Type 1 HAE. Acute treatment with Berinert was successful, and the patient was later placed on long-term prophylaxis with lanadelumab, which is a monoclonal antibody that inhibits Kallikrein. This case illustrates the importance of considering HAE in children with unexplained abdominal symptoms, particularly in the context of a family history of the condition. Early identification and treatment are essential to managing this life-threatening disorder.

PMID:40617599 | DOI:10.1136/bcr-2024-263989

Immunol Res. 2025 Jul 5;73(1):104. doi: 10.1007/s12026-025-09660-3.

ABSTRACT

22q11.2 deletion syndrome (22qDS) is a heterogeneous genetic disorder associated with a variety of clinical manifestations, including congenital heart disease, neuropsychiatric disorders, hypocalcemia, and immunological deficiencies. This study aimed to characterize the clinical and immunological features of patients with 22qDS in a cohort from Colombia. We conducted a retrospective study over a 3-year period, including 40 patients with confirmed 22qDS. Demographic, clinical, and immunological data were collected from medical records. The cohort had a median age of 3 years, with a balanced sex distribution. Heart defects were present in 75% of patients, followed by ear and craniofacial abnormalities (50%) and language disorders (45%). Immunological work-up revealed low T cell subsets in 42% of patients, with a decrease in T cell lymphopenia observed with age. Humoral deficiencies were also common, with 20% of patients exhibiting selective IgM deficiency and 17% presenting with hypogammaglobulinemia. Recurrent infections were observed in 48% of patients, particularly pneumonia and otitis. Vaccine responses to protein-based antigens and polysaccharides were frequently impaired. The findings highlight the clinical and immunological heterogeneity of 22qDS in this Latin American cohort. Multidisciplinary care, early diagnosis, and immunological management are essential for improving outcomes in these patients.

PMID:40615621 | DOI:10.1007/s12026-025-09660-3

Sage Open Pediatr. 2025 Jun 20;12:30502225251346345. doi: 10.1177/30502225251346345. eCollection 2025 Jan-Dec.

ABSTRACT

OBJECTIVES: This study investigated the clinical features, treatment approaches, and outcomes of severe Bacille Calmette-Guérin (BCG) vaccine complications in Chinese children.

INTRODUCTION: BCG is the only available vaccine for tuberculosis (TB) prevention but can cause serious complications such as local abscesses, lymphadenitis, and disseminated BCG. Research on their management in China is limited.

METHODS: This observational study reviewed 95 children with severe BCG-related complications treated at a tuberculosis-specialized hospital in Guangdong, China (2016-2020). Of these, 33 (34.7%) had injection site reactions, 55 (57.9%) developed lymphadenitis with 31 suppurative cases, and 7 (7.4%) had disseminated BCG. All deep abscesses and suppurative lymphadenitis were successfully treated with surgery and anti-tubercular therapy. Two disseminated BCG cases had primary immunodeficiency, and 1 of them died.

CONCLUSION: Most local reactions respond to conservative treatment. Surgery combined with anti-tubercular therapy is effective for suppurative lymphadenitis. Early immunological evaluation is essential for disseminated disease.

PMID:40612176 | PMC:PMC12220855 | DOI:10.1177/30502225251346345

Semin Ultrasound CT MR. 2025 Jul 1:S0887-2171(25)00038-1. doi: 10.1053/j.sult.2025.06.005. Online ahead of print.

ABSTRACT

Pulmonary lymphoproliferative disorders (PLDs) are a diverse group of rare entities characterized by abnormal lymphoid proliferation within the lung. These include both benign and malignant processes and are classified into five categories in the 2021 WHO Classification of Thoracic Tumors: benign hyperplastic disorders, primary pulmonary neoplasms, secondary involvement of the lung, posttransplant lymphoproliferative disorders, and histiocytic neoplasms. Diagnosing PLDs is often challenging due to their histological similarity to other lymphocyte-rich interstitial lung diseases, including cellular nonspecific interstitial pneumonia (NSIP) and hypersensitivity pneumonitis. A multidisciplinary approach integrating clinical, radiologic, and pathological information is essential to reach an accurate diagnosis. This review focuses on the detailed pathological features of PLDs, particularly benign hyperplastic disorders and primary pulmonary neoplasms. It emphasizes the differential diagnosis and highlights distinguishing characteristics among key subtypes, including lymphoid interstitial pneumonia, follicular bronchiolitis, nodular lymphoid hyperplasia, Castleman disease, IgG4-related disease, and primary pulmonary lymphomas such as MALT lymphoma, diffuse large B-cell lymphoma, and lymphomatoid granulomatosis. Special attention is paid to morphological patterns, immunophenotypes, and diagnostic challenges encountered with small biopsies. Given the broad differential diagnosis and potential overlap with infectious, autoimmune, or immunodeficiency-related conditions, careful clinicopathological correlation remains the cornerstone of accurate classification and appropriate management. This review aims to enhance diagnostic clarity and support effective interdisciplinary evaluation of suspected PLD cases.

PMID:40609772 | DOI:10.1053/j.sult.2025.06.005

Mycoses. 2025 Jul;68(7):e70086. doi: 10.1111/myc.70086.

ABSTRACT

BACKGROUND: Chronic Granulomatous Disease (CGD) is a rare primary immunodeficiency, predisposing to life-threatening invasive mould infection (IMI). While antifungal prophylaxis has improved outcomes, IMI remains the leading cause of mortality in CGD. This study aimed to evaluate the clinical and fungal epidemiology of IMI among CGD patients in Türkiye and explore diagnostic and treatment challenges.

METHODS: Demographics, clinical characteristics, IMI episodes, diagnostic methods, and antifungal prophylaxis regimens of 72 CGD patients followed at the Division of Paediatric Immunology of Marmara, Cerrahpaşa and Çukurova University School of Medicine, Türkiye between 1991 and 2022 were analysed. IMI episodes were classified as proven, probable, or possible based on the European Organisation for Research and Treatment of Cancer/Mycoses Study Group criteria.

RESULTS: Of the patients, 79.1% were male, and 52.8% had autosomal-recessive CGD (AR-CGD). Forty-two IMI episodes were detected in 39 (54.2%) patients, predominantly involving the lungs. Proven IMI accounted for 28.5% of episodes, with Aspergillus fumigatus as the most frequent pathogen. Patients with X-linked CGD experienced earlier IMI onset than AR-CGD (34.0 months (IQR: 18.0-65.5) versus 122.0 months (IQR: 40.25-240.0; p = 0.005)). Presentation with IMI led to the CGD diagnosis in 20 (51.3%) patients, while 19 (48.7%) developed IMI under itraconazole prophylaxis (median: 96.0 months, IQR: 48.0-153.0). Of 13 deaths (18.0%), 84.6% were associated with IMI.

CONCLUSIONS: Our study highlights the persistently high burden of IMI among CGD patients, despite antifungal prophylaxis. Challenges in diagnosis, including limited access to invasive biopsy and diagnostic modalities, and gaps in prophylactic monitoring, underscore the need for optimised management strategies.

PMID:40607896 | DOI:10.1111/myc.70086

Front Immunol. 2025 Jun 18;16:1586288. doi: 10.3389/fimmu.2025.1586288. eCollection 2025.

ABSTRACT

INTRODUCTION: Acute hemorrhagic leukoencephalitis (AHLE) is a rare, fulminant neuroinflammatory disease with high mortality rate. It most often occurs after infections; however, the exact etiology of the disease remains unclear. We highlight that complement factor I (FI) deficiency may be a possible cause of AHLE.

CASE REPORT: We describe a 9-year-old patient presenting with fever, headache, dizziness, ataxia, and diplopia, who developed rapid neurologic decline and refractory intracranial pressure elevation. Based on clinical, laboratory, and MRI findings, AHLE was diagnosed. Successful treatment included therapeutic plasma exchange (PEX) and early decompressive craniectomy. At one year of follow-up, the patient showed complete recovery. Complement testing of the patient revealed complete FI deficiency. Genetic workup uncovered a germline pathogenic variant in the CFI gene.

DISCUSSION: As AHLE is an emerging phenotype of complement FI deficiency, with only a few previously reported cases in the literature, high clinical suspicion and awareness among clinicians are needed. To control the complement system, prompt blockade with complement FI substitution via PEX and early decompressive craniectomy may be life-saving. In neuroinflammatory diseases with unknown etiology, complement testing is recommended.

PMID:40607425 | PMC:PMC12213424 | DOI:10.3389/fimmu.2025.1586288

Mol Ther Methods Clin Dev. 2025 Jun 2;33(3):101502. doi: 10.1016/j.omtm.2025.101502. eCollection 2025 Sep 11.

ABSTRACT

Myotonic dystrophy type 1 (DM1) is caused by a (CTG) _n expansion in the DMPK gene, leading to a multisystemic manifestation and broad disease presentation. Although the DM1 phenotype and onset correlate with expansion length, understanding DM1 etiology and developing effective therapies remains challenging. Here, we investigated the contribution of repeat length on aberrant splicing and response to antisense oligonucleotides (ASOs). In primary DM1 myoblasts bearing repeat lengths of 800, 1,200, or >3,000, DMPK downregulation was achieved by blocking and gapmer ASOs, though splicing correction was inefficient. Further analyses revealed profound differences in DMPK mRNA levels. To exclude such confounding effects, we generated an isogenic myoblast panel with repeats from 0 to 2,900 triplets using a repeat-targeted CRISPR/Cas9 nickase approach. This panel revealed repeat-length dependency of aberrant splicing and nuclear MBNL1 abundance. While the blocker ASO marginally induced DMPK downregulation with longer repeats, its effect on splicing correction was evident, though decreased as repeat length increased. The gapmer ASO led to substantial downregulation and essentially normalized splicing levels throughout. Our study demonstrates that repeat length is central to therapeutic effectiveness, but this correlation may be obscured by genetic background, underscoring the need to consider genotypic heterogeneity in DM1 clinical trials.

PMID:40606545 | PMC:PMC12221585 | DOI:10.1016/j.omtm.2025.101502

BMC Oral Health. 2025 Jul 2;25(1):1017. doi: 10.1186/s12903-025-06359-7.

ABSTRACT

BACKGROUND: The factors causing acute attacks during dental and gingival procedures in patients with hereditary angioedema due to C1 inhibitor (HAE-C1INH) deficiency remain unclear. Our aim is to investigate the patients and dental/gingival procedure characteristics influencing acute attack risk.

METHODS: A retrospective review of 638 dental interventions in 40 HAE-C1INH patients was conducted between June and September 2023 using questionnaires, diaries, and medical charts. Data included demographics, clinical details, intervention history, and types of procedures, aiming to understand acute attack patterns.

RESULTS: A total of 40 HAE-C1INH patients (36 type 1; 23 female; median age 41.5 (30.8-53.5) years; median disease onset age 10.5 (5.0-15.0) years; median annual attack frequency 24.5 (12.0-52.0) were analyzed. Facial and laryngeal edema history were found in 82.5% and 67.5% of patients, respectively. Treatment-naive median serum C4 level, C1 inhibitor (C1INH) function and C1INH antigenic level (for type 1 HAE) were 6 mg/dL (IQR: 5-6; normal range: 10-40 mg/dL), 13.2% (IQR: 7.2-18.8; normal range: 70-130%), and 5.6 mg/dL (IQR: 3-7; normal range: 0.21-0.39 g/L), respectively. Acute angioedema attacks were observed in 72 out of 638 procedures. Before HAE-C1INH diagnosis, per-person attack frequency and per-procedure attack frequency were found to be 26.5% (9/34), and 15.74% (95% CI:12.28-19.71), respectively. Higher annual attack frequency (p = 0.038), lower C1INH function (p = 0.044), and female gender (p = 0.047) related to acute attacks due to dental interventions in pre-diagnosis period. Prophylactic HAE treatment significantly reduced the frequency of acute attacks following dental procedures. The attack frequency per procedure was 14.6% (95% CI: 11.48-18.20) among untreated patients and 3.23% (95% CI: 1.19-6.89) among those receiving prophylactic medication, post-diagnosis. Tooth extraction, wisdom teeth extraction and challenging surgical tooth extraction were found to be more risky.

CONCLUSION: Prophylactic HAE treatment significantly reduced the frequency of acute attacks, compared to the untreated group. Pre-procedural prophylactic treatment is particularly important for safer dental care in HAE patients with higher annual attack frequency, lower C1INH function, and female gender, especially during high-risk procedures such as tooth extraction, wisdom teeth extraction, and challenging surgical tooth extractions.

PMID:40604794 | DOI:10.1186/s12903-025-06359-7

Clin Infect Dis. 2025 Jul 2:ciaf344. doi: 10.1093/cid/ciaf344. Online ahead of print.

ABSTRACT

BACKGROUND: Immunocompromised patients are often excluded from pneumonia trials, guidelines, and stewardship interventions.The objective of this study was to evaluate whether empiric broad-spectrum antibiotic treatment impacts mortality and other clinical outcomes in moderately immunocompromised patients without risk factors for multidrug-resistant organisms hospitalized with community-acquired pneumonia.

METHODS: This was a target trial emulation including moderately immunocompromised (asplenia, hematologic malignancies, solid organ malignancy receiving chemotherapy, kidney transplant >1 year prior, congenital/acquired immunodeficiency and receiving immunosuppressive medications) patients with pneumonia without risk factors for multidrug-resistant organisms at 69 hospitals in the Michigan Hospital Medicine Safety ConsortiumThis study compared the receipt of empiric broad-spectrum antibiotics against antibiotics targeting typical respiratory pathogens on hospital day 1 or 2.The primary outcome was mortality. Secondary outcomes included length of stay, transfer to the intensive care unit and 30-day readmission, emergency department visit, Clostridioides difficile infection and antibiotic-associated adverse events.

RESULTS: Of 2706 moderately immunocompromised patients with pneumonia, 59% (N=1596) received empiric broad-spectrum antibiotics. MRSA and resistant gram-negative bacteria were rare (94/2706, 3.5%). After adjustment, empiric broad-spectrum antibiotic treatment was not associated with mortality, but was associated with readmission (adjusted hazard ratio [aHR], 1.32 [1.05-1.66]), transfer to ICU (aHR, 2.65 [1.32-5.30]) and longer hospitalization (adjusted rate ratio [aRR], 1.14 [1.10-1.19]).

CONCLUSIONS: Immunocompromised patients hospitalized with pneumonia often receive empiric broad-spectrum antibiotics despite low rates of multidrug-resistant organisms. Empiric broad-spectrum antibiotic use was not associated with mortality, but was associated with harm, including 30-day readmission, transfer to ICU and longer duration of hospitalization.

PMID:40601818 | DOI:10.1093/cid/ciaf344

Front Immunol. 2025 Jun 17;16:1596971. doi: 10.3389/fimmu.2025.1596971. eCollection 2025.

ABSTRACT

INTRODUCTION: The International Patient Organisation for Primary Immunodeficiencies (IPOPI) held its third edition of the Global Multi-Stakeholders’ Summit, gathering key primary immunodeficiencies (PID) stakeholders and experts to discuss and foment global collaboration.

METHODS: This edition focused on the impact of genomic medicine in PID treatment, the role of digital health, including artificial intelligence, in PID care, and how to anticipate and minimise risks to ensure optimal patient access to care.

RESULTS: These discussions aimed to examine current hurdles and brainstorm feasible solutions and priorities for the PID community in these areas in the next ten years.

DISCUSSION: These discussions led to recommendations for comprehensive approaches to care and access to treatment for PID patients, suggesting actions that will bring the community closer to treatments based on real-world evidence and adjusted to patient’s needs. To accomplish this, collaboration between academia, industry, regulatory authorities, and patients is crucial.

PMID:40599777 | PMC:PMC12209282 | DOI:10.3389/fimmu.2025.1596971