Eosinophilic granulomatosis with polyangiitis (EGPA), until recently called Churg-Strauss syndrome is a systemic necrotizing vasculitis with multiple organ involvement, most commonly manifested by asthma, eosinophilia and necrotizing extravasal granulomas. Anti-neutrophil cytoplasmic autoantibodies (ANCA) are found in some of the patients. EGPA is one of the rarest forms of primary systemic vasculitis.Since the first description of the disease in 1951, its classification has undergone many changes aimed at refining the diagnostic process and timely treatment. In order to be diagnosed precisely, patients must meet certain criteria. The lack of a unified approach in the application of these criteria, as well as the overlap of clinical symptoms with other primary systemic vasculitides, make it difficult to study EGPA epidemiology.This publication aims to analyze epidemiological data on EGPA and to provide an assessment of the incidence and prevalence of this disease in Bulgaria. Read the whole article here.
The aim of this study is to systematize and analyze the available evidence on the financial burden of comorbidities in patients with acromegaly. A literature search was conducted in the scientific databases PubMed, Google Scholar, Bioseek using predefined keywords. Studies have been selected on the basis of their primary goal. 16 studies were included in the qualitative synthesis based on screening of 176 identified studies in the databases. Most of the selected studies were conducted in the USA (n = 6), Canada (n = 2), Sweden (n = 2), China (n = 1), Spain (n = 1), Italy (n = 1), Poland (n = 1). Studies confirmed the financial burden of comorbidities, which is most significant in patients with poor control of acromegaly/or of the main diesease – almost 2 times higher than in patients with good control. The costs of concomitant diseases vary in different countries and depend on the type of disease, as their share is lower than pharmacotherapy cost for acromegaly – 25% compared to 75%. The use of appropriate pharmacotherapy (octreotide, pasireotide) for acromegaly leads to reduction in the incidence and severity of comorbidities and to cost savings. Effective and timely control of comorbidities in acromegaly could lead to achievement of the desired long-term therapeutic results, reduction of overall mortality, improvement of quality of life, as well as reduction in total treatment costs from the point of view of the society and health care system. Read the whole article here.
Central hypoventilation syndrome (or Ondine–Hirschprung disease) is a rare autosomal dominant disease caused by heterozygous mutation in the PHOX2B gene on chromosome 4p13. It is characterized by a deficiency in autonomic control of respiration, which results in inadequate or ventilatory responses to hypercapnia and hypoxemia.Authors present a 4 years and 3 months boy monitored from birth. In the early neonatal period the neurological symptoms were respiratory pauses and apnea, muscle hypotonia, neonatal seizures. Magnetic resonance imaging of head showed periventricular and intraventricular hemorragies, periventricular leukomalacia. Complementary were found respiratory distress syndrome, bilateral nephrocalcinosis, secondary defect type foramen ovale with left-right shunt, sinus arythmia with often sinus pauses, isolated auricular extrasystoles, gastroesophageal reflux, facial dysmorphysm. DNA analysis of the PHOХ2B gene showed heterozygous frameshift mutation of exon 3, duplication18p6, which leads to expansion of 6 alanin residues (26 alanins) in the terminal С-terminal end of the PHOX2B gene.A complex lifesaving therapy was proceeded in the neonatal period. To the age of 3 years the patient was left at home on spontaneous breathing with tracheostoma and ventilation at night. After the removal of the tracheostoma the patient continues noninvasive ventilation at night. Read the whole article here.
The new issue of our scientific journal Rare Diseases and Orphan Drugs is now online. The issue contains 5 publications on various topics. The editorial is “Economic modeling in health technology assessment – what is acceptable and what makes sense?”.
The assessment of health technologies and the subsequent decision to pay with public funds focus on the concept of value and more precisely on the added clinical and economic value compared to the existing and available alternatives for comparison. The greater the added value of a new health technology, the more likely is the acceptance of a positive reimbursement recommendation. Measuring added value is not a problem because there is a wide range of research tools to accomplish this task. However, the evaluation of added value is problematic. Very often there are no clear criteria of what minimum result is needed for a positive recommendation to pay for new health technology with public funds. Moreover, assessment is a highly subjective process and the various stakeholders in it – doctors, patients, payers and industry – often have divergent positions on the same issue. This fundamental problem illustrates the need to use economic modeling in health technologies assessment and deciding to pay with public funds. Read the whole article here.
Osteogenesis imperfecta (OI), also known as “brittle bone disease”, is a rare genetic disorder of the skeleton, whose most benign form I corresponds to autosomal dominant mutations in the genes encoding type I collagen (COLA1, COLA2). Several associated skeletal manifestations are often observed but, surprisingly, while dentin defects often reflect genetic bone disorders, about half of OI patients have no obvious oral manifestations. Here, we investigated the collagen, mineral and mechanical properties of dentin from deciduous teeth collected from patients with mild form of OI and displaying no obvious clinical signs of dentinogenesis imperfecta. For the first time, an increase in the hardness of OI dentin associated with an increase in mineral content compared to healthy patients was reported. In addition, OI altered the tissue characteristics of the dentin-enamel junction but the interfacial gradient was preserved. The impact of changes in molecular structure due to mutations in OI was assessed by Raman microspectroscopy. Our results highlighted a change in the hydroxyproline-proline ratio in direct association with collagen mineralization. Our findings suggest that the evaluation of teeth could be an important aid for mild types of OI that are often difficult to diagnose clinically and provide experimental evidence that hydroxyproline content should be considered in future studies on collagen-based biomaterials. Read the whole article here.
Genodermatoses are heritable skin diseases that can cause significant morbidity and mortality. Most of them show characteristic cutaneous findings. Genodermatoses can be associated with extracutaneous system abnormalities. Diagnosing hereditary skin disorders is still a challenging task due to their rarity and diversity, due to diseases evolving over many years, and the initial manifestations not always being diagnostic; therefore, ongoing evaluation and surveillance is often required to make the accurate diagnosis. The algorithm for the diagnosis depends on a combination of thorough clinical and family history clinical examination, laboratory findings, consultation of multiple medical specialists, and molecular analysis. Diagnostic testing targeted at differentiation of similar genodermatoses may be required. Recognition is crucial for the initiation of the treatment for skin manifestations and detection of other extracutaneous abnormalities, including malignancy. Diagnostic accuracy and molecular diagnosis may help in providing a template for ongoing management, testing, and education and prognostication for families of children with genodermatoses. Read the whole article here.
The Bulgarian Hemophilia Association organizes an information campaign on the occasion of the World Hemophilia Day – April 17. The campaign will be held under the title “We are moving together with the change!”, and the association calls on everyone who wish to join the dissemination of information materials that will be published through their communication channels.
By bringing together as many people as possible in this year’s hashtag campaign on social media #движимсезаедноспромяната and #световенденахемофилията the association aims first to inform the general public about all the specifics of the disease and the needs of each patient in times of isolation and global pandemic, calling on everyone to be together in this new reality.
More information about the campaign can be found at the following link: https://hemo-bg.org/
8th annual symposium “HEALTH TECHNOLOGY ASSESSMENT – STRATEGIES FOR ACCELERATED ACCESS”, 27 March 2021
On 27 March 2021 was held the 8th annual symposium “HEALTH TECHNOLOGY ASSESSMENT – STRATEGIES FOR ACCELERATED ACCESS, organized by the Institute for Rare Diseases. For the first year, the event took place online in the digital platform Virtual Congress Venue, thus facilitating interactive discussions between participants from different countries such as the UK, Singapore, Slovakia, Romania, Czech republic, etc. Experts from Israel, Spain, France, Poland, Switzerland and Bulgaria shared their global, country-specific, academic and regulatory experience in international reference pricing, negotiation of discounts and rebates and managed entry agreements. The main topics of the discussions were health technology assessment, sustainable access to innovative therapies within limited budgets, as well as decision-making tools.
Information on topics and speakers at: https://vcv.raredis.org/en/event/health-technology-assessment-strategies-for-accelerated-access/
Vitamin D is a fat-soluble steroid hormone playing a pivotal role in calcium and phosphate homeostasis as well as in bone health. Vitamin D levels are not exclusively dependent on food intake. Indeed, the endogenous production-occurring in the skin and dependent on sun exposure-contributes to the majority amount of vitamin D present in the body. Since vitamin D receptors (VDRs) are ubiquitous and drive the expression of hundreds of genes, the interest in vitamin D has tremendously grown and its role in different diseases has been extensively studied. Several investigations indicated that vitamin D action extends far beyond bone health and calcium metabolism, showing broad effects on a variety of critical illnesses, including cancer, infections, cardiovascular and autoimmune diseases. Epidemiological studies indicated that low circulating vitamin D levels inversely correlate with cutaneous manifestations and bone abnormalities, clinical hallmarks of neurofibromatosis type 1 (NF1). NF1 is an autosomal dominant tumour predisposition syndrome causing significant pain and morbidity, for which limited treatment options are available. In this context, vitamin D or its analogues have been used to treat both skin and bone lesions in NF1 patients, alone or combined with other therapeutic agents. Here we provide an overview of vitamin D, its characteristic nutritional properties relevant for health benefits and its role in NF1 disorder. We focus on preclinical and clinical studies that demonstrated the clinical correlation between vitamin D status and NF1 disease, thus providing important insights into disease pathogenesis and new opportunities for targeted therapy. Read the whole article here.
Mastocytosis is a rare disease characterised by expansion and collection of clonal mast cells in various organs including the skin, bone marrow, spleen, lymph nodes and gastrointestinal tract. The prevalence of mastocytosis has been estimated to be one in 10 000, while the estimated incidence is one per 100 000 people per year. Cutaneous mastocytosis is classified into (i) maculopapular cutaneous mastocytosis, also known as urticaria pigmentosa; (ii) diffuse cutaneous mastocytosis; and (iii) mastocytoma of the skin. In adults, cutaneous lesions are usually associated with indolent systemic mastocytosis and have a chronic evolution. Paediatric patients, on the contrary, have often cutaneous manifestations without systemic involvement and usually experience a spontaneous regression. Diagnosis of cutaneous mastocytosis may be challenging due to the rarity of the disease and the overlap of cutaneous manifestations. This short review describes pathogenesis and clinical aspects of cutaneous mastocytosis with a focus on diagnosis and currently available therapies. Read the whole article here.