Curr Opin Oncol. 2025 May 1;37(3):250-258. doi: 10.1097/CCO.0000000000001141. Epub 2025 Mar 19.

ABSTRACT

PURPOSE OF REVIEW: Rare cancers of the genitourinary (GU) tract are often clinically aggressive yet have few or no standard-of-care treatments. Multiple antibody-drug conjugates (ADCs) have been approved in solid malignancies. This review explores the use of ADCs in rare GU tumors in the context of biological pathways and ongoing research in solid tumors.

RECENT FINDINGS: Few clinical trials of ADCs focus on recruiting participants with rare tumors of the GU tract, including trials testing enfortumab vedotin as monotherapy or combined with pembrolizumab, and sacituzumab govitecan as monotherapy or combined with atezolizumab. We highlight many ongoing trials of novel ADCs for advanced/metastatic solid tumors and emphasize the potential eligibility of patients with rare GU tumors for tumor-agnostic trials.

SUMMARY: ADCs are being tested in multiple solid tumors, including rare GU tumors. Ongoing preclinical research supports the use of some ADCs in several rare GU tumors and improves our understanding of their pathophysiology.

PMID:40110990 | DOI:10.1097/CCO.0000000000001141

Zhongguo Dang Dai Er Ke Za Zhi. 2025 Mar 15;27(3):373-376. doi: 10.7499/j.issn.1008-8830.2409076.

ABSTRACT

The patient is a male neonate born at term. He was admitted 16 minutes after birth due to stridor and inspiratory respiratory distress. Physical examination revealed a cleft palate, and a grade II systolic ejection murmur was audible at the left sternal border. Whole exome sequencing identified a heterozygous variant in the SON gene, c.5753-5756del (p.Val1918GlufsTer87), which was absent in either parent, indicating a de novo mutation. According to the guidelines of the American College of Medical Genetics and Genomics, this was classified as a "pathogenic variant" leading to a diagnosis of Zhu-Tokita-Takenouchi-Kim (ZTTK) syndrome. Upon admission, symptomatic supportive treatment was provided. Follow-up at the age of 8 months revealed persistent stridor; the infant could only consume small amounts of milk and was unable to sit steadily. This patient represents the youngest reported case to date, and his symptoms expand the clinical spectrum of the disease, providing valuable insights for clinical diagnosis and treatment.

PMID:40105086 | DOI:10.7499/j.issn.1008-8830.2409076

Arq Neuropsiquiatr. 2025 Feb;83(2):1-6. doi: 10.1055/s-0045-1804920. Epub 2025 Mar 19.

ABSTRACT

BACKGROUND: Patients with neuromuscular diseases (NMDs) often face swallowing difficulties (dysphagia) as part of their condition.

OBJECTIVE: To determine the prevalence of self-reported swallowing disorders in patients with rare NMDs and examine their correlation with related quality of life (QoL).

METHODS: The study included 103 patients with confirmed rare NMDs. Dysphagia risk was assessed using the validated Eating Assessment Tool-10 (EAT-10), and QoL related to swallowing was measured with the SWAL-QoL survey. Correlations between EAT-10 and SWAL-QoL scores were analyzed. Additionally, the mean questionnaire scores were compared among patients classified as dysphagic, dysphagic with high aspiration risk, and nondysphagic.

RESULTS: The estimated prevalence of dysphagia in the cohort, based on EAT-10, was 52.4%. Higher scores were significantly correlated with poorer swallowing-related QoL, except for the sleep domain. The most affected SWAL-QoL domains were burden, eating desire, eating duration, food selection, communication, fear, mental health, social functioning, and dysphagia battery score (DBS), with significant differences observed among the classifications (p < 0.001 for most domains, and p = 0.015 for eating desire). No statistically significant difference in swallowing QoL was found between sitters and walkers.

CONCLUSION: Dysphagia is a prevalent symptom in patients with rare NMDs, affecting 52.4% of the cohort and significantly impacting QoL in nearly all domains except sleep.

PMID:40107292 | DOI:10.1055/s-0045-1804920

Tokai J Exp Clin Med. 2025 Apr 20;50(1):34-36.

ABSTRACT

A 19-year-old woman with three seborrheic keratosis on her right abdomen and five seborrheic keratosis on her both buttocks is presented. That developed at the age of five and two months prior to the visit. At our initial dermatological examination, we noticed three oval, well defined, brown tumors on her right abdomen, and several round, well defined, brown nodules on her both buttocks. Dermoscopy findings showed comedo-like openings, fissures, and ridges. Histopathological examination showed hyperkeratosis and pseudohorn cysts, and basaloid keratinocytes proliferation with no dysplastic cells. These findings were consistent with SK. She was treated by cryotherapy using a liquid nitrogen spray, and her tumors and nodules dropped off entirely. Juvenile-onset of seborrheic keratosis is quite rare in East Asian countries and needs to be differentiated from keratinocytic epidermal nevus.

PMID:40105231

Rev Salud Publica (Bogota). 2023 Jul 1;25(4):107594. doi: 10.15446/rsap.V25n4.107594. eCollection 2023 Aug.

ABSTRACT

OBJECTIVE: To analyze the reports of orphan diseases in Bogotá, in order to describe the epidemiological profile, based on the cases reported to the Public Health System (Sivigila), from January 2019 to March 2022.

METHODS: A descriptive and cross-sectional study was carried out in which the cases reported to Sivigila in Bogotá were analyzed in the period between January 2019 and March 2022. Absolute and relative frequencies, frequency distribution and prevalences and averages of different variables were calculated. notified in the notification sheets.

RESULTS: From January 2019 to March 2022, 10,399 patients with orphan diseases have been notified to Sivigila in Bogotá, of which 56.25% (5,849) are female and 43.75% (4,550) are female. male sex. 87.10% (9,060) of the cases belong to the contributory regime. The town with the highest number of reports was Suba with 15.85% (1,294). The most reported orphan diseases were: multiple sclerosis with 13.1% (1,363), amyotrophic lateral sclerosis with 4.04% (421) and Guillain-Barre syndrome with 3.6% (374). A patient with an orphan disease in Bogotá takes 61.3 months on average from the beginning of their symptoms to obtaining a diagnosis (SD 101.9).

CONCLUSIONS: From the notification to Sivigila in Bogotá, compared to the global prevalence, there is an under-registration of patients with orphan diseases and the delay in the diagnosis of these diseases is evident.

PMID:40098659 | PMC:PMC11648384 | DOI:10.15446/rsap.V25n4.107594

bioRxiv [Preprint]. 2025 Mar 8:2025.03.03.641186. doi: 10.1101/2025.03.03.641186.

ABSTRACT

Amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), and Alzheimer's disease (AD) are common neurodegenerative disorders for which the mechanisms driving neuronal death remain unclear. Single-cell whole-genome sequencing of 429 neurons from three C9ORF72 ALS, six C9ORF72 FTD, seven AD, and twenty-three neurotypical control brains revealed significantly increased burdens in somatic single nucleotide variant (sSNV) and insertion/deletion (sIndel) in all three disease conditions. Mutational signature analysis identified a disease-associated sSNV signature suggestive of oxidative damage and an sIndel process, affecting 28% of ALS, 79% of FTD, and 65% of AD neurons but only 5% of control neurons (diseased vs. control: OR=31.20, p = 2.35×10-10). Disease-associated sIndels were primarily two-basepair deletions resembling signature ID4, which was previously linked to topoisomerase 1 (TOP1)-mediated mutagenesis. Duplex sequencing confirmed the presence of sIndels and identified similar single-strand events as potential precursor lesions. TOP1-associated sIndel mutagenesis and resulting genome instability may thus represent a common mechanism of neurodegeneration.

PMID:40093130 | PMC:PMC11908196 | DOI:10.1101/2025.03.03.641186

bioRxiv [Preprint]. 2025 Mar 4:2025.03.03.641217. doi: 10.1101/2025.03.03.641217.

ABSTRACT

Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease that is linked to exposure to repetitive head impacts (RHI), yet little is known about its pathogenesis. Applying two single-cell whole-genome sequencing methods to hundreds of neurons from prefrontal cortex of 15 individuals with CTE, and 4 with RHI without CTE, revealed increased somatic single-nucleotide variants in CTE, resembling a pattern previously reported in Alzheimer's disease (AD). Furthermore, we discovered remarkably high burdens of somatic small insertions and deletions in a subset of CTE individuals, resembling a known pattern, ID4, also found in AD. Our results suggest that neurons in CTE experience stereotyped mutational processes shared with AD; the absence of similar changes in RHI neurons without CTE suggests that CTE involves mechanisms beyond RHI alone.

PMID:40093089 | PMC:PMC11908173 | DOI:10.1101/2025.03.03.641217

bioRxiv [Preprint]. 2025 Mar 6:2025.03.05.641682. doi: 10.1101/2025.03.05.641682.

ABSTRACT

A mechanistic understanding of neurodevelopment requires us to follow the multiscale processes that connect molecular genetic processes to macroscopic cerebral cortical formations and thence to neurological function. Using magnetic resonance imaging of the brain of the ferret, a model organism for studying cortical morphogenesis, we create in vitro physical gel models and in silico numerical simulations of normal brain gyrification. Using observations of genetically manipulated animal models, we identify cerebral cortical thickness and cortical expansion rate as the primary drivers of dysmorphogenesis and demonstrate that in silico models allow us to examine the causes of aberrations in morphology and developmental processes at various stages of cortical ontogenesis. Finally, we explain analogous cortical malformations in human brains, with comparisons with human phenotypes induced by the same genetic defects, providing a unified perspective on brain morphogenesis that is driven proximally by genetic causes and affected mechanically via variations in the geometry of the brain and differential growth of the cortex.

PMID:40093050 | PMC:PMC11908256 | DOI:10.1101/2025.03.05.641682

Tunis Med. 2025 Feb 5;103(2):212-216. doi: 10.62438/tunismed.v103i2.5261.

ABSTRACT

INTRODUCTION: Lipoid pneumonia is a rare disease affecting adults' which frequency increases with age. Exogenous lipoid pneumonia results from the penetration, usually by inhalation, of oily substances into the pulmonary parenchyma.

AIM: To study the clinical and radiological features of exogenous lipoid pneumonia and to define therapeutic strategies.

METHODS: We performed a monocentric, retrospective study of patients followed in the Pneumology Department of the Hedi Chaker Hospital in Sfax between 2004 and 2023. The diagnosis of exogenous lipoid pneumonia was confirmed by bronchoalveolar lavage with positive Oil Red O staining or by biopsy with anatomopathological examination showing lipid-laden foamy histiocytes.

RESULTS: During this period, we collected nine patients with an average age of 46. Dyspnea and cough were the most frequent symptoms. Chest computed tomography revealed ground-glass opacity in five cases, parenchymal condensations in three cases and crazy paving in three cases. The frequent risk factors were occupational exposure to a lipid in five cases and consumption of a lipid product in four cases. In terms of treatment, four patients underwent occupational reclassification and a declaration of occupational disease. Systemic corticotherapy was indicated in six patients.

CONCLUSION: Exogenous lipoid pneumonia is a rare entity. This study highlights the difficulty of making a diagnosis, due to misleading clinico-radiological presentation in the absence of exposure.

PMID:40096721 | DOI:10.62438/tunismed.v103i2.5261

J Mol Cell Biol. 2025 Mar 17:mjaf009. doi: 10.1093/jmcb/mjaf009. Online ahead of print.

ABSTRACT

Calciphylaxis is a rare, progressive disorder characterized by subcutaneous adipose and dermal microvascular calcifications, microthrombi, and endothelial damage. It mainly affects patients with chronic kidney disease (CKD), which is also known as calcific uremic arteriolopathy. Skin biopsy is the gold standard for diagnosis, but it is an invasive procedure. Calciphylaxis frequently results in ischemic and nonhealing ulcerations with a high mortality rate. A multidisciplinary targeted approach is the primary treatment method. Vascular calcification, which is a common complication in patients with CKD, cannot completely explain the rapid progression of calciphylaxis. This article reviews the advances in the epidemiological characteristics, risk factors, and diagnosis, including non-uraemic calciphylaxis (NUC) and visceral calciphylaxis, pathogenesis, associated animal models, and treatment of calciphylaxis. The scarcity of animal models that mimic the clinical presentation of calciphylaxis hampers the understanding of its pathogenesis. The acute effects on progressive vascular injury, including the induction of severe ischemia and inflammatory responses, have been emphasized. Actively listening to the voices of patients and their families and building a multidimensional research system with artificial intelligence technologies based on the specific molecular makeup of calciphylaxis patients will help tailor regenerative treatment strategies. Mesenchymal stem cells (MSCs) may be proposed as a novel therapy for calciphylaxis because of their regenerative effects, inhibition of vascular calcification, anti-infection and immunomodulation properties, and improvement of hypercoagulability. Safe, effective, accessible, and economical MSC strategies guided by biomarkers deserve consideration for the treatment of this devastating disease.

PMID:40097288 | DOI:10.1093/jmcb/mjaf009

J Assoc Physicians India. 2025 Mar;73(3):11-12. doi: 10.59556/japi.73.0884.

ABSTRACT

Guillain-Barré syndrome (GBS) is a rare but common cause of acute flaccid paralysis globally.1 This syndrome, first described in 1916 by Georges Guillain, Jean Alexandre Barré, and André Strohl, has captured the interest of clinicians, researchers, and patients all over the world.2.

PMID:40087924 | DOI:10.59556/japi.73.0884

Skelet Muscle. 2025 Mar 15;15(1):7. doi: 10.1186/s13395-025-00376-4.

ABSTRACT

BACKGROUND: SELENON-Congenital Myopathy (SELENON-CM) is a rare congenital myopathy caused by mutations of the SELENON gene characterized by axial muscle weakness and progressive respiratory insufficiency. Muscle histopathology may be non-specific, but commonly includes multiminicores or a dystrophic pattern. The SELENON gene encodes selenoprotein N (SelN), a selenocysteine-containing redox enzyme located in the endo/sarcoplasmic reticulum membrane where it colocalizes with mitochondria-associated membranes. However, the molecular mechanism(s) by which SelN deficiency cause SELENON-CM remain poorly understood. A hurdle is the lack of cellular and animal models that show easily assayable phenotypes.

METHODS: Using CRISPR-Cas9 we generated three zebrafish models of SELENON-CM, which were then studied by spontaneous coiling, hatching, and activity assays. We also performed selenon coexpression analysis using a single cell RNAseq zebrafish embryo-atlas. SelN-deficient myoblasts were generated and assayed for glutathione, reactive oxygen species, carbonylation, and nytrosylation levels. Finally, we tested Selenon-deficient myoblasts' metabolism using a Seahorse cell respirometer.

RESULTS: We report deep-phenotyping of SelN-deficient zebrafish and muscle cells. SelN-deficient zebrafish exhibit changes in embryonic muscle function and swimming activity in larvae. Analysis of single cell RNAseq data in a zebrafish embryo-atlas revealed coexpression of selenon and genes involved in the glutathione redox pathway. SelN-deficient zebrafish and mouse myoblasts exhibit altered glutathione and redox homeostasis, as well as abnormal patterns of energy metabolism, suggesting roles for SelN in these functions.

CONCLUSIONS: These data demonstrate a role for SelN in zebrafish early development and myoblast metabolism and provide a basis for cellular and animal model assays for SELENON-CM.

PMID:40087793 | DOI:10.1186/s13395-025-00376-4

Orphanet J Rare Dis. 2025 Mar 14;20(1):125. doi: 10.1186/s13023-025-03614-6.

ABSTRACT

BACKGROUND: Clinical trials for rare diseases pose unique challenges warranting alternative approaches in demonstrating treatment efficacy. Such trials face challenges including small patient populations, variable onset of symptoms and rate of disease progression, and ethical considerations, particularly in neurodegenerative diseases. In this study, we present the retrospective clinical global impression (RCGI) severity and change (RCGI-S/C) scale on 27 patients with GM1 gangliosidosis, a post hoc clinician-rated outcome measure to evaluate natural history study participants as historical controls for comparisons with treated patients in a clinical trial.

METHODS: We conducted a systematic chart review of 27 GM1 gangliosidosis natural history participants across 95 total visits. RCGI-S was assessed at the first visit and rated 1 (normal) to 7 (among the most extremely ill). Each subsequent follow-up was rated on the RCGI-C scale from 1 (very much improved) to 7 (very much worse). We demonstrate scoring guidelines of both scales with examples and justifications for this pilot in GM1 gangliosidosis natural history participants. The convergent validity of the RCGI scales was explored through correlations with magnetic resonance imaging (MRI) and the Vineland Adaptive Behavioral Scales.

RESULTS: We found strong association between the RCGI-S scores with gray matter volume (r(14) = -0.81; 95% CI [-0.93, -0.51], p < 0.001), and RCGI-C scores significantly correlated with increases in ventricular volume (χ2(1) = 18.6, p < 0.001). Baseline RCGI-S scores also strongly correlated with Vineland adaptive behavioral composite scores taken at the same visit (r(14) = -0.72; 95% CI [-0.93, -0.17], p = 0.02).

CONCLUSION: RCGI-S/C scales, which use the clinical evaluation to assess the severity of disease of each patient visit over time, were consolidated into a single quantitative metric in this study. Longitudinal RCGI-C scores allowed us to quantify disease progression in our late-infantile and juvenile GM1 patients. We suggest that the retrospective CGI may be an important tool in evaluating historical data for comparison with changes in disease progression/mitigation following therapeutic interventions.

PMID:40087722 | DOI:10.1186/s13023-025-03614-6

BMC Bioinformatics. 2025 Mar 14;26(1):82. doi: 10.1186/s12859-025-06096-2.

ABSTRACT

BACKGROUND: Diagnosing Mendelian and rare genetic conditions requires identifying phenotype-associated genetic findings and prioritizing likely disease-causing genes. This task is labor-intensive for molecular and clinical geneticists, who must review extensive literature and databases to link patient phenotypes with causal genotypes. The challenge is further complicated by the large number of genetic variants detected through next-generation sequencing, which impacts both diagnosis timelines and patient care strategies. To address this, in silico methods that prioritize causal genes based on patient-derived phenotypes offer an effective solution, reducing the time involved in diagnostic case reviews and enhancing the efficiency of clinical diagnosis.

RESULTS: We developed the phenotype prioritization and analysis for rare diseases (PPAR) to rank genes based on human phenotype ontology (HPO) terms, with the specific goal of aiding the interpretation of genetic testing for Mendelian and rare diseases. PPAR leverages embeddings from a knowledge graph and incorporates knowledge from connections between genes, HPO terms, and gene ontology annotations. When applied on a clinical rare disease cohort and the publicly available deciphering developmental disorders (DDD) dataset. PPAR ranked the causal gene in the top 10 for 27% of cases in the clinical cohort and for 85% of cases in the DDD dataset, outperforming other established HPO-based methods.

CONCLUSION: Our findings demonstrate that PPAR, a method developed from the clinical knowledge graph, effectively ranks causal genes based on patient-derived HPO terms in rare and Mendelian disease contexts. PPAR has shown superior performance compared to other well-established HPO-only methods and provides an efficient, accessible solution for clinical geneticists. The Python-based tool is publicly available at https://github.com/dimi-lab/PPAR , offering a user-friendly platform for gene prioritization.

PMID:40087567 | DOI:10.1186/s12859-025-06096-2

Nat Commun. 2025 Mar 14;16(1):2500. doi: 10.1038/s41467-025-57695-9.

ABSTRACT

With ongoing improvements in the detection of complex genomic and epigenomic variations, long-read sequencing (LRS) technologies could serve as a unified platform for clinical genetic testing, particularly in rare disease settings, where nearly half of patients remain undiagnosed using existing technologies. Here, we report a simplified funnel-down filtration strategy aimed at enhancing the identification of small and large deleterious variants as well as abnormal episignature disease profiles from whole-genome LRS data. This approach detected all pathogenic single nucleotide, structural, and methylation variants in a positive control set (N = 76) including an independent sample set with known methylation profiles (N = 57). When applied to patients who previously had negative short-read testing (N = 51), additional diagnoses were uncovered in 10% of cases, including a methylation profile at the spinal muscular atrophy locus utilized for diagnosing this life-threatening, yet treatable, condition. Our study illustrates the utility of LRS in clinical genetic testing and the discovery of novel disease variation.

PMID:40087273 | DOI:10.1038/s41467-025-57695-9

Mol Genet Metab. 2025 Apr;144(4):109073. doi: 10.1016/j.ymgme.2025.109073. Epub 2025 Mar 1.

ABSTRACT

Rare diseases affect over 400 million people worldwide, with approved treatment available for less than 6 % of these diseases. Drug repurposing is a key strategy in the development of therapies for rare disease patients with large unmet medical needs. The process of repurposing drugs compared to novel drug development is a time-saving and cost-efficient method potentially resulting in higher success rates. To accelerate and ensure sustainability in therapy development for rare neurometabolic, neurological, and neuromuscular diseases, an international consortium SIMilarities in clinical and molecular PATHology (SIMPATHIC) has been established where we move away from the one drug one disease concept and move towards one drug targeting a pathomechanism shared between diseases, by applying parallel preclinical and clinical drug development. Here the consortium describes accelerators of drug repurposing pursued by the consortium, including 1) co-creation, 2) patient empowerment, 3) use of standardized induced pluripotent stem cell (iPSC)-derived disease models and cellular and molecular profiling, 4) high-throughput drug screening in neurons, 5) innovative clinical trial design, and 6) selection of appropriate exploitation and patient access models. In this way, a fast and effective drug repurposing pathway for several rare diseases will be established to reduce time from discovery to patient access.

PMID:40086177 | DOI:10.1016/j.ymgme.2025.109073

Front Public Health. 2025 Feb 27;13:1417771. doi: 10.3389/fpubh.2025.1417771. eCollection 2025.

ABSTRACT

Burnout among physicians has gained increasing attention in recent years. This issue arises not only from stressful working conditions and individual factors but also from the correlation between burnout and physicians' tolerance of uncertainty. This association could be particularly important in the context of rare diseases, which inherently present greater uncertainty. To date, no studies have explored this topic. Our exploratory study aimed to investigate the associations between uncertainty and burnout scores among physicians while considering secondary factors associated with rare diseases and COVID-related stress. Although not the primary focus, we included COVID-related stress due to its impact during the ongoing pandemic. We conducted an online survey using the Physicians' Reaction to Uncertainty Scale (PRU) and the Oldenburg Burnout Inventory (OLBI). Experience with rare diseases was quantified by assessing the weekly working hours devoted to patients with such conditions. We conducted a path analysis, initially using a fully recursive model and subsequently eliminating non-significant paths. 128 physicians (n = 73 female) participated in the survey, with 31% of them displaying significant burnout scores. Notably, significant associations were found between the PRU subscale anxiety and both dimensions of burnout, as well as between the PRU subscale disclosure to patients and the burnout dimension of exhaustion. COVID-related stress was also significantly associated with exhaustion, while experience with rare diseases was significantly associated with disengagement. No correlation was observed between experience with rare diseases and uncertainty scores. The model demonstrated an excellent fit (RMSEA = 0.055). Our results show that physician burnout is a pressing issue and confirm the association between anxiety due to uncertainty and increased burnout scores.

PMID:40084205 | PMC:PMC11903758 | DOI:10.3389/fpubh.2025.1417771

Front Public Health. 2025 Feb 26;13:1510818. doi: 10.3389/fpubh.2025.1510818. eCollection 2025.

ABSTRACT

BACKGROUND: Undiagnosed rare diseases (URDs) are a complex and multifaceted challenge, especially in low-and medium-income countries. They affect individuals with unique clinical features and lack a clear diagnostic label. Although the Undiagnosed Diseases Network International (UDNI) definition of URDs is not universally accepted, it is widely recognized.

METHODS: We surveyed UDNI members and participants from other countries to explore the challenges posed by URDs and identify possible solutions. Participation in the survey was completely voluntary.

RESULTS: The survey revealed a need for more consensus on a universally accepted definition for URDs. Still, the UDNI definition gained widespread recognition and serves as a valuable framework for understanding and addressing the challenges of URDs. In addition to national or international networks, fostering a more substantial engagement and resource-sharing ethos among member countries is critical. Despite advances in genomics and diagnostic tools, the diagnostic journey for people living with URDs (PLURDs) remains arduous and often inconclusive. The availability of specialized centers and the utilization of whole exome sequencing (WES) and whole genome sequencing (WGS) vary across countries, with disparities due to healthcare systems, economic status, and government policies. Advocacy groups play a crucial role in supporting PLURDs.

CONCLUSION: A unified commitment to prioritizing URDs on the global health agenda, paired with targeted funding, stipulated national strategies, and aligned international cooperation, is imperative to leveling the playing field for the diagnosis and management of URDs and capitalizing on the potential of Advocacy Groups as allies in this endeavor.

PMID:40078755 | PMC:PMC11897027 | DOI:10.3389/fpubh.2025.1510818

Rheumatology (Oxford). 2025 Mar 1;64(Supplement_1):i82-i84. doi: 10.1093/rheumatology/keae593.

ABSTRACT

Polyarteritis Nodosa (PAN), is the firstly described vasculitis and can be seen in paediatric and adult age. PAN has a heterozygous clinical picture including cutaneous, constitutional, musculoskeletal, gastrointestinal, and renal involvement. Description and splitting of other vasculitis, makes this medium vessel vasculitis, a very rare disease. Additionally, many subgroups of PAN have been defined and this effort let to move Hepatitis B virus-PAN to Vasculitis with probable aetiology. Anyhow, idiopathic PAN still exists and cohorts from various countries such as France, India, and Japan have been published. Rarity of PAN necessities global collaboration to highlight clinical features and genetics studies. GLOBAL-PAN is an ongoing collaborative project of EUVAS, VCRC and many national cohorts. This review covers the recent epidemiological data of PAN along with demographic and clinical characteristics of cohorts from all-over the world and GLOBAL-PAN.

PMID:40071408 | DOI:10.1093/rheumatology/keae593

Orphanet J Rare Dis. 2025 Mar 11;20(1):117. doi: 10.1186/s13023-025-03618-2.

ABSTRACT

BACKGROUND: The current development of gynecology services for children and adolescents seeks to meet needs both in the overall population and in patients with rare diseases. In France, the referral center for rare gynecological diseases specializes in four major types of conditions, namely, uterovaginal malformations, hereditary hemorrhagic diseases, rare benign breast diseases, and gynecological repercussions of rare chronic diseases.

OBJECTIVE: To describe consecutive patients who had a first visit in 2018-2023 at the referral center for rare gynecological diseases at the Necker Pediatric University Hospital in Paris, France, and who were diagnosed with a condition in any of the four categories listed above.

MATERIAL AND METHODS: For this single-center retrospective observational cohort study, data from the referral-center database were collected and reviewed. These data included year of birth, age at and reason for first gynecology visit, and rare chronic disease and referring rare-disease center for patients seen for gynecological repercussions of rare chronic diseases.

RESULTS: The 704 included patients had a median age of 15.2 years (interquartile range 3.8) at the first visit. Among them, 100 (14.2%) had uterovaginal malformations, 32 (4.6%) hereditary hemorrhagic diseases, 17 (2.4%) rare benign breast diseases, and 555 (78.8%) gynecological repercussions of rare chronic diseases. The leading reasons for the visit were dysmenorrhea (15.6%), menorrhagia (15.5%), uterovaginal malformations (15.2%), and irregular periods (14.9%).

CONCLUSION: Repercussions of rare chronic diseases managed at rare-disease referral centers were by far the leading reason for seeking gynecological expertise in rare diseases. In this complex situation, the underlying disease and its treatments interact with the gynecological manifestations and their treatment, requiring close collaboration among all specialists caring for each patient.

PMID:40069734 | DOI:10.1186/s13023-025-03618-2