Traditional Chinese medicine (TCM) has increasingly attracted the attention of researchers as a potential complementary or supportive approach for selected rare diseases, but the characteristics and evidentiary strength of this literature remain unclear. This Correspondence summarizes publication patterns identified for the 121 conditions in the First Chinese Rare Disease List using Chinese and English sources searched from database inception through June 30, 2021. Fifty-five rare diseases were identified in 3,030 TCM-related publications, though the ten most frequently studied conditions accounted for more than 80% of the literature. Generalized myasthenia gravis, idiopathic pulmonary fibrosis, and multiple sclerosis together accounted for nearly half of all publications. Clinical studies and case reports or experience summaries predominated, whereas experimental studies represented only 9.03%. Oral herbal formulas were the most frequently reported intervention, and more than 95% of publications originated from mainland China. These patterns indicate growing interest but a fragmented, geographically concentrated, and methodologically limited evidence base; publication volume should not be interpreted as evidence of efficacy or safety. Future research should prioritize mechanistic studies, standardized and innovative clinical designs, rigorous safety and quality-control procedures, real-world evidence, patient-centered outcomes, and international collaboration to clarify the potential roles and limitations of TCM in rare disease management.
Japan's designated intractable disease (nanbyo) framework combines a population threshold with unresolved pathogenesis or treatment, long-term care needs, objective diagnostic criteria, and severity-linked assistance with medical expenses. We conducted a targeted narrative review of official Japanese sources and biomedical literature through August 3, 2026. Evidence ranged from regulatory approvals and randomized trials to observational, case-report, and preclinical data, so therapeutic maturity was assessed separately from mechanistic plausibility. We distinguished the 12 official skin/connective-tissue entries from six purposively selected designated entries or disease groups with decisive cutaneous phenotypes or Japan-specific translational value. The resulting 18-entry framework is illustrative, not exhaustive. It highlights Japan-specific biology or evidence regarding xeroderma pigmentosum, acquired idiopathic generalized anhidrosis, DPP-4 inhibitor-related bullous pemphigoid, generalized pustular psoriasis, cold-medicine-related SJS/TEN, anti-MDA5 dermatomyositis, and Nakajo-Nishimura syndrome. Recently approved indications or uses include dupilumab for adult bullous pemphigoid, IL-36 receptor blockade, topical COL7A1 gene delivery, autologous gene-corrected epidermal sheets, MEK inhibition, IL-1 blockade, and topical mTOR inhibition; JAK-interferon strategies remain investigational. We contend that Japan's designation infrastructure could become an interoperable translational platform linking natural-history cohorts, endotype-defined enrollment, mechanism-aligned endpoints, and multinational adaptive trials.
Fragile X syndrome (FXS) is the most common genetic cause of inherited intellectual disabilities. Individuals with full mutation of FXS exhibit physical and behavioral symptoms in addition to other comorbidities. The clinical features of FXS have been widely studied in Caucasians; however, they remain limited in the Asian population. This study aimed to characterize the spectrum and variability of physical and behavioral phenotypes in Asian populations. A total of 5,830 studies from the PubMed, ScienceDirect, Scopus, and Cochrane/CENTRAL databases were screened using the Covidence software. We identified FXS-specific research studies conducted in Asia that reported the clinical characteristics of individuals with FXS. This review summarizes 51 studies from different Asian regions. The frequently reported physical characteristics were large and prominent ears (72.63%), an elongated face (57.49%), and macroorchidism (45.21%). The three most prevalent behavioral characteristics were intellectual disability (ID), hyperactivity, and social withdrawal, reported in 99%, 77%, and 55% of all cases, respectively. Our findings show that the physical characteristics of FXS are variable in the Asian group but similar to those in other populations and are not recommended for early recognition. Individuals with intellectual disabilities, especially when combined with autism spectrum disorders and large prominent ears, are suggestive of further genetic testing for FXS.
Joubert syndrome (JS) is a rare ciliopathy characterized by neurological and multisystem manifestations; however, skeletal involvement remains poorly recognized. We report two genetically confirmed pediatric patients with JS illustrating different degrees of bone impairment. The first patient, a 2.5-year-old boy with a TMEM67 mutation, presented with severe hypotonia, profound immobility, multiple fractures, and markedly reduced bone mineral density (DXA Z-score -5.875), fulfilling the criteria for secondary osteoporosis and requiring bisphosphonate therapy. The second patient, a 5-year-old girl with an OFD1 mosaic mutation, showed delayed motor development and reduced bone mineral density (DXA Z-score -2.2) without fractures and was managed conservatively. These cases demonstrate the broad spectrum of skeletal manifestations in JS, ranging from low bone mineral density to severe secondary osteoporosis. Reduced mobility and chronic hypotonia may contribute to impaired bone mineralization. Increased awareness and early bone health surveillance, including fracture assessment and densitometric evaluation, may facilitate timely diagnosis and improve management of bone complications in patients with Joubert syndrome.
Fulminant myocarditis (FM) is a severe, rapidly progressive and life-threatening condition of myocarditis associated with infectious or autoimmune etiologies. Here, we present three patients with an invasive thymoma who had FM, which eventually led to sudden death. The most frequent clinical presentations at onset include palpitations, orthopnea, and acute worsening of myasthenia gravis (MG). Highly elevated myocardial biomarkers and positive autoantibodies against cardiac muscle, skeletal muscle, and neuromuscular junctions were detected in serum. The electrocardiograph (ECG) findings progressed to life-threatening ventricular arrhythmias. Although high-dose methylprednisolone or intravenous immunoglobulin was administered along with advanced respiratory support, profound hemodynamic collapse rapidly occurred, and these patients eventually died within days. This case series underscores the importance of rapid recognition of FM associated with thymoma and early aggressive supportive and immunomodulatory interventions, including consideration of mechanical circulatory support when clinically indicated.
Rare diseases pose a persistent challenge to healthcare systems worldwide due to their low prevalence, high treatment costs, and rapid emergence of novel therapies. In China, while significant progress has been made through national rare disease lists and medical insurance negotiations, substantial medical security gaps remain at the subnational level. This Policy Forum examines the decade-long evolution of rare disease-specific medical security policies in Zhejiang Province (2015-2025) to draw broader lessons for designing sustainable and equitable coverage mechanisms under centralized insurance systems. Using the multiple streams framework (MSF) as an interpretive lens, this article puts forth three policy arguments. First, medical security for rare diseases cannot rely solely on basic medical insurance (BMI); instead, it requires institutional layering that combines insurance-based pooling, fiscal instruments, and social co-assistance. Second, in highly centralized governance contexts, policy entrepreneurship is predominantly state-embedded, with administrative agencies playing a decisive role in coupling problems, solutions, and political mandates. Third, policy innovation in relation to rare diseases is not a one-time event but an iterative process, in which each reform generates new problem definitions and policy windows. The Zhejiang experience demonstrates that under institutional constraints such as standardized benefit lists, local governments can achieve strategic innovation within the available institutional space by shifting their policy focus from reimbursing costs for "drugs on the Nationally Reimbursed Drug List (NRDL)" to targeted compensation for expenditures for drugs not on the NRDL. This pathway improves treatment affordability while maintaining fiscal sustainability, providing actionable insights for China and healthcare systems in other countries facing similar structural constraints.
Rare diseases pose a persistent challenge to healthcare systems worldwide due to their low prevalence, high treatment costs, and rapid emergence of novel therapies. In China, while significant progress has been made through national rare disease lists and medical insurance negotiations, substantial medical security gaps remain at the subnational level. This Policy Forum examines the decade-long evolution of rare disease-specific medical security policies in Zhejiang Province (2015-2025) to draw broader lessons for designing sustainable and equitable coverage mechanisms under centralized insurance systems. Using the multiple streams framework (MSF) as an interpretive lens, this article puts forth three policy arguments. First, medical security for rare diseases cannot rely solely on basic medical insurance (BMI); instead, it requires institutional layering that combines insurance-based pooling, fiscal instruments, and social co-assistance. Second, in highly centralized governance contexts, policy entrepreneurship is predominantly state-embedded, with administrative agencies playing a decisive role in coupling problems, solutions, and political mandates. Third, policy innovation in relation to rare diseases is not a one-time event but an iterative process, in which each reform generates new problem definitions and policy windows. The Zhejiang experience demonstrates that under institutional constraints such as standardized benefit lists, local governments can achieve strategic innovation within the available institutional space by shifting their policy focus from reimbursing costs for "drugs on the Nationally Reimbursed Drug List (NRDL)" to targeted compensation for expenditures for drugs not on the NRDL. This pathway improves treatment affordability while maintaining fiscal sustainability, providing actionable insights for China and healthcare systems in other countries facing similar structural constraints.
International collaboration is indispensable in rare diseases, yet its depth and impact vary widely. In recent years, China has expanded its engagement in global rare-disease initiatives, but not all efforts translate into lasting progress. This Policy Forum examines China's evolving role through the lens of symbolic versus substantive collaboration. While symbolic efforts enhance visibility, substantive collaboration builds durable infrastructures-such as standardized terminologies, interoperable data systems and registries, and sustained clinical and research networks. Drawing on policy-relevant case examples, this article shows how patient-centered, infrastructure-building approaches can transform episodic engagement into systemic capacity. Looking ahead, the next phase of collaboration must focus on embedding global standards into health information systems, registries, and reimbursement frameworks. With its population scale, growing scientific capacity, and expanding global interaction, China is well positioned to evolve from a participant to a co-shaper of a truly global rare-disease ecosystem.
There is controversial evidence that some selected congenital anomalies (CA) are associated with sex, maternal age, urban-rural residence, or socioeconomic status among the Hispanic population. This study aimed to assess the prevalence and maternal-child clinical and socioeconomic factors across a wide range of CA in a hospital-based setting from northwest Mexico. From January to December 2023, a cross-sectional study for CA and live births at Durango General Hospital was performed. Hospital-based prevalence was calculated for all CA subtypes and grouped anatomical system defects. Associations with CA and subgroup analysis were conducted to assess newborn sex, maternal age, residence, and socioeconomic factors on CA prevalence, using Pearson's chi-squared test and Fisher's exact test. Probability of CA was estimated based on logistic regression analysis along with odds ratio (OR) and its 95% confidence interval. All tests were two-sided with p values < 0.05 considered statistically significant. A total of 6,784 newborns and 306 CA were assessed (hospital-based prevalence 4.5%). Males, maternal age < 20 and ≥ 35 years, urban residence, and lowest socioeconomic status were associated with CA (all OR > 1.0 and p < 0.05). Subgroup analysis indicated associations between males and cardiovascular and genitourinary defects; maternal age < 20 years and craniofacial and abdominal defects; maternal age ≥ 35 years and digestive and chromosomal abnormalities; mother's urban residence and craniofacial, cardiovascular, genitourinary, and abdominal defects; socioeconomic levels D-E and craniofacial and cardiovascular defects (all OR > 1.0 and p < 0.05). These findings reflect noticeable components associated with several CA and might be relevant for prevention and maternal-child health.
Globally, the prevention and treatment of rare diseases is still constrained by limited diagnostic and therapeutic capacity, restricted drug accessibility, and disparities in medical security systems. In response, China has developed a distinct "China Model" of rare disease governance, characterized by national policy leadership and coordinated local implementation. This study systematically reviews policies issued between 2009 and 2026 and it analyzes five domains: i) prevention and screening, ii) list-based governance, iii) clinical diagnosis and treatment systems, iv) drug accessibility, and v) payment guarantees. Shandong Province is examined as a representative case. Findings show that the central government has established unified standards through two nationally endorsed rare disease lists covering 207 conditions, supported by clinical guidelines and a national collaborative network for diagnosis and treatment of those diseases. Regulatory incentives for drug review and approval have facilitated the inclusion of 126 treatments for patients with rare diseases in the National Basic Medical Insurance reimbursement list, forming an integrated policy framework spanning identification, diagnosis, treatment, and financial protection. At the provincial level, Shandong is aligned with national directives by integrating its case registration system with the national platform, enhancing quality control across its clinical network and developing a multilevel payment mechanism. The core of the "China Model" is the enhancement of clinical capacity through standardized systems and networked organizations, combined with multilevel risk-sharing mechanisms. However, governance challenges persist, including weak inter-organizational policy coordination, barriers to drug accessibility, fragmented coverage schemes, and an underdeveloped data governance infrastructure. Addressing these challenges requires enhanced end-to-end policy implementation and institution of effective local practices at the national level.
Congenital extrahepatic portosystemic shunts (CEPS) are rare congenital vascular malformations characterized by an abnormal communication between the hepatic portal venous system and the systemic venous system. Type Ⅱ CEPS preserves partial portal venous blood flow and can usually be treated with conventional surgery rather than solely relying on liver transplantation. To determine the optimal surgical methods and complication management strategies for type Ⅱ CEPS patients, we retrospectively analyzed 31 predominantly adult patients with type Ⅱ CEPS, documenting their surgical approaches and the occurrence of postoperative complications. Five surgical approaches were employed: 11 patients underwent shunt occlusion with 5 cases of complications; 5 patients underwent splenic vessels ligation with 2 cases of complications; 5 patients underwent shunt occlusion combined with splenic artery ligation with 4 cases of complications; 8 patients underwent shunt occlusion combined with distal splenorenal shunt with 3 cases of complications; and 2 patients with lower extremity edema underwent inferior vena cava shunt bypass surgery, with no significant complications observed. In conclusion, surgery centering on the shunt occlusion demonstrates promising therapeutic value and remains the mainstay in the treatment of type II CEPS. Meanwhile, postoperative complications remain a concern, necessitating long-term monitoring and management.
To quantitatively describe the disease burden and living status of patients with primary immunodeficiency (PID) in China, a descriptive, nationwide cross-sectional survey was conducted in September 2024 via a patient organization, yielding 435 valid responses. Among respondents, 82% were male and 77% were pediatric; antibody deficiencies were the most common category (63%), with X-linked agammaglobulinemia (49%) being the most frequent self-reported subtype. The mean diagnostic delay was 3 years, with 45.2% waiting over 1 year and 78.6% experiencing prior misdiagnosis or missed diagnosis. Although 82% received immunoglobulin therapy, only 7% reported being relatively healthy without complications. Health-related quality of life (HRQoL) utility values, measured via EQ-5D instruments, were 0.87 for children and 0.84 for adults, appearing lower than reference population norms. Educational disruption affected 25.1% of pediatric patients, while 27% of adult patients were unemployed and 47.1% required frequent sick leave. Caregiving demands were extensive, with 53.4% of pediatric patients requiring dedicated care, resulting in 51.5% of their primary caregivers resigning from their jobs. In conclusion, PID imposes substantial medical, psychological, and socioeconomic burdens in China. These descriptive findings highlight an urgent need for earlier diagnosis, improved therapeutic access, and integrated societal support systems for education, employment, and caregiving.
This review characterizes VEXAS syndrome (Vacuoles, E1 enzyme, X-linked, Autoinflammatory, Somatic) as a prototype of adult-onset autoinflammation that challenges traditional autoimmune paradigms. Driven by constitutive activation of innate myeloid cells via Ubiquitin-Like Modifier Activating Enzyme 1 (UBA1) mutations, VEXAS affects the nervous system in approximately 6-10% of cases. We identify the peripheral nervous system as the primary target (70%), typically manifesting as refractory axonal polyneuropathy, while central involvement may present as neutrophilic meningoencephalitis. Crucially, we highlight the "hematologic paradox"-hyperinflammation co-occurring with macrocytic anemia rather than thrombocytosis-as the key biomarker distinguishing VEXAS from vasculitic mimics, necessitating early genetic sequencing for targeted clone suppression.
Chimeric antigen receptor (CAR) T-cell therapy targeting B cells has emerged as a breakthrough treatment for hematological malignancies and shows promising potential in autoimmune diseases. While selective targeting of B-cell activation and autoantibody production represents an innovative therapeutic approach in autoimmune conditions, clinical responses remain suboptimal in many patients due to incomplete B-cell depletion in tissues and limitations in identifying ideal target antigens. Over the past four years, autologous or allogeneic CAR T-cell therapy has demonstrated remarkable efficacy in autoimmune diseases, achieving rapid and sustained B-cell depletion alongside complete clinical and serological remission. This review examines the current landscape of B cell-targeting CAR T-cell therapy, its therapeutic applications in autoimmune disorders, ongoing translational research, and future developments.
Dementia prevention increasingly requires attention to modifiable systemic inflammatory stressors. In older adults, bullous pemphigoid (BP), herpes zoster (HZ), psoriasis, atopic dermatitis (AD), rosacea, prurigo nodularis (PN), and chronic pruritus are not merely disorders limited to the skin; they may signal or amplify neuroimmune vulnerability. Observational studies link BP with dementia and Alzheimer's disease, HZ with incident dementia and vascular cognitive injury, and psoriasis, AD, rosacea, or PN with smaller but biologically plausible cognitive risks. The proposed skin-brain axis integrates cytokine spillover, endothelial activation, blood-brain barrier dysfunction, BP180/ BP230 autoantigen sharing, varicellazoster virus neurotropism and vasculopathy, barrier failure, dysbiosis, itching-induced fragmented sleep, and medication or frailty-related cognitive toxicity. Clinically, cognitive impairment also worsens skin surveillance, hygiene, topical adherence, and recognition of pain, itching, infection, or blistering. Although causality and dementia prevention remain unproven, the evidence justifies proactive dermatological care in older adults and greater cognitive vigilance in older patients with severe inflammatory or pruritic dermatoses. Recombinant zoster vaccination, prompt antiviral therapy, steroid-sparing BP strategies, modern anti-inflammatory treatment for AD, psoriasis, and PN, and systematic attention to sleep, itching, caregiver capacity, and the medication burden are practical, low-regret steps while prospective brain-relevant trials are developed. This translational framework highlights mechanisms clinicians can now interrupt and endpoints investigators can soon measure. We propose that the skin should be recognized as a sentinel organ for neurodegeneration and that dermatological disease represents a potentially modifiable contributor to cognitive decline.
Rare diseases represent a significant public health challenge in China, affecting an estimated 20 million individuals. Despite incremental policy improvements over the past decade, including the publication of two National Rare Disease Lists, an increasing number of available treatments, and the inclusion of some therapies in the Nationally Reimbursed Drug List (NRDL), patients continue to face systemic challenges in diagnosis, treatment access, and sustainable protection. That said, China has very limited rare disease research & development (R&D) and industrial development, so the market potential is far from being tapped. This policy review argues that the lack of a national legal definition for rare diseases and orphan drugs, an unsustainable payment mechanism for high-value innovative therapies, and insufficient incentives for domestic research and development have collectively hindered the creation of a sustainable rare disease ecosystem. Drawing on an analysis of patient registry data, policy documents, and proposals from China's National People's Congress (NPC) sessions, we demonstrate a growing societal consensus on the need for comprehensive national legislation on rare diseases, which is not only a moral imperative to safeguard the rights of patients but also a strategic necessity for a national population strategy and biomedical industrial development. We consider systemic rare disease legislation in China to be imperative, and now is the optimal time to promote rare disease legislation in China. We propose nine key initiatives, including establishment of a working committee on national legislation, creating a standardized definition of rare diseases and orphan drugs, creating a dedicated national rare disease fund, and robust R&D incentives.
The high costs of diagnosing and treating rare diseases impose a substantial financial burden on patients and families, underscoring the need to understand reimbursement experiences and unmet needs to improve medical security. Using Dravet syndrome, a severe and lifelong epileptic encephalopathy, as a representative rare disease, this study conducted an online questionnaire survey completed by 161 respondents, including family members or caregivers of patients with Dravet syndrome. The results revealed that most families had insufficient income to cover treatment costs, with patients' annual treatment expenses generally approaching or even exceeding their families' financial capacity, while 41.67% reported that out-of-pocket payments after reimbursement accounted for more than half of their total treatment expense. Surveyed respondents expressed general satisfaction with various medical security models (over 75%), including basic medical insurance, critical illness insurance, medical assistance, commercial health insurance, and charitable aid. However, challenges remain: the limited funding pool and reimbursement capacity of basic medical insurance, the ongoing development of commercial insurance products (e.g., region-specific Huimin insurance), and the lack of guaranteed scale and sustainability of charitable funding. Thus, further improvements in China's medical security for rare disease are imperative. Key priorities include enhancing policy coherence, improving coordination across security models, and increasing the depth of coverage at all levels to alleviate the financial burden on patients.
Fabry disease (FD) is a rare multisystemic lysosomal storage disorder with diverse pediatric manifestations. This multicenter study analyzed 64 children with FD from the Chinese Children Genetic Kidney Disease Database following establishment of the first national pediatric FD multidisciplinary team (MDT) in April 2020, which expanded to 15 centers by January 2022. Median diagnostic age was 11.4 years in males and 9.4 years in females, with diagnostic delays of 4.4 and 4.0 years, respectively. Family screening accounted for most female diagnoses (72.2%), while 6.5% of males were incidentally detected during genetic testing for other diseases. Missense variants predominated (65.2% males, 66.7% females). Biochemically, males had markedly reduced α-Gal A activity (0.6 ±0.4 μmol/L/h), and most patients showed elevated globotriaosylsphingosine (Lyso-GL-3), including 87.0% of males and 83.3% of females. Neuropathic pain was the most common initial symptom (52.2% males, 27.8% females; median onset 8 years), primarily acroparesthesia (92.1% and 85.7%, respectively). Other frequent features included anhidrosis/hypohidrosis (58.7% males, 11.1% females). Multisystem involvement included cardiac (arrhythmia n = 11, left ventricular hypertrophy n = 3), pulmonary (obstructive airway disease in 24.2% of males), skeletal (low bone mineral density in 4/7 tested males), and renal manifestations (reduced glomerular filtration rate (GFR) in 3). Thirty-seven patients received enzyme replacement therapy at median ages of 12.9 years (males) and 11.7 years (females). This first nationwide pediatric FD cohort highlights substantial diagnostic delays and underscores the importance of MDT collaboration, family screening, and early recognition to improve outcomes in affected children.
Neuromyelitis optica spectrum disorder (NMOSD) is a relapsing autoimmune disorder predominantly driven by anti-aquaporin-4 immunoglobulin G (AQP4-IgG), which mediates astrocyte injury, neuroinflammation, and demyelination. Satralizumab and Inebilizumab represent two promising therapeutic options with distinct mechanisms of action and clinical profiles. This study conducted a retrospective pharmacovigilance analysis of data from the U.S. FDA Adverse Event Reporting System (FAERS) from January 2020 to June 2025 to assess and compare adverse event (AE) reporting signals associated with Satralizumab and Inebilizumab. The analysis revealed a higher number of reported adverse events for Satralizumab compared to Inebilizumab (1,114 cases vs. 349 cases). A higher reporting proportion of AEs was observed in female patients for both drugs, with no statistically significant difference between them (exploratory p = 0.760). The reported AEs for both agents were primarily categorized under System Organ Classes (SOCs) such as infections and infestations and nervous system disorders. Urinary tract infection and pneumonia were among the most frequently reported preferred terms (PTs) for Satralizumab, whereas headache and COVID-19 were prominent for Inebilizumab. Reports classified as serious were more frequent for Satralizumab than for Inebilizumab (exploratory p < 0.01), noting that "seriousness" in FAERS may encompass outcomes related to underlying disease activity. This signal detection study highlights distinct adverse event reporting profiles for these biologics and offers insights that may inform clinical monitoring and personalized treatment strategies in NMOSD. Further studies with rigorous prospective designs are recommended to validate these findings and elucidate the mechanisms underlying the observed adverse events.
For the vast rare disease patient community in China, science communication is crucial for bridging the information gap. However, the traditional, expert-led knowledge distribution model has proven insufficient to address the dual challenges of resource scarcity and low efficiency in the rare disease field. This paper introduces a new science communication model derived from practice in China. With "Patient-Driven Co-Creation" as its core, this model's ultimate goal transcends traditional information dissemination, aiming to empower the entire ecosystem through systematic value creation. Through an analysis of the practical model of the Wonder Sir platform, this paper proposes for the first time the "Patient Compounding Value Model". This model demonstrates how intangible patient-lived experiences can be systematically transformed into tangible assets capable of driving scientific research, clinical optimization, and public policy, thereby providing a sustainable value-generation mechanism for the resource-scarce rare disease field.
