Rare Disease In Europe Research Articles

A case of pulmonary melioidosis in Germany: a rare differential diagnosis in returning travelers from South-East Asia

BackgroundMelioidosis is a bacterial infection associated with high mortality. The diagnostic approach to this rare disease in Europe is challenging, especially because pulmonary manifestation of melioidosis can mimic pulmonary tuberculosis (TB). Antibiotic therapy of melioidosis consists of an initial intensive phase of 2–8 weeks followed by an eradication therapy of 3–6 months.Case presentationWe present the case of a 46-year-old female patient with pulmonary melioidosis in Germany. The patient showed chronic cough, a pulmonary mass and a cavitary lesion, which led to the initial suspicion of pulmonary TB. Melioidosis was considered due to a long-term stay in Thailand with recurrent exposure to rice fields.ResultsMicrobiologic results were negative for TB. Histopathology of an endobronchial tumor showed marked chronic granulation tissue and fibrinous inflammation. Melioidosis was diagnosed via polymerase chain reaction by detection of Burkholderia pseudomallei/mallei target from mediastinal lymph-node tissue.ConclusionThis case report emphasizes that melioidosis is an important differential diagnosis in patients with suspected pulmonary tuberculosis and recent travel to South-East Asia.

Intraductal papillary neoplasms of the bile ducts: a comparative study of a rare disease in Europe and Nagoya, Japan

BackgroundIntraductal papillary neoplasm of the bile ducts (IPNB) is a rare disease in Western countries. The aim of this study was to compare tumor characteristics, management strategies, and outcomes between Western and Eastern patients who underwent surgical resection for IPNB. MethodsA multi-institutional retrospective series of patients with IPNB undergoing surgery between January 2010 and December 2020 was gathered under the auspices of the European-African Hepato-Pancreato-Biliary Association (E-AHPBA), and at Nagoya University Hospital, Japan. ResultsA total of 85 patients (51% male; median age 66 years) from 28 E-AHPBA centers were compared to 91 patients (64% male; median age 71 years) from Nagoya. Patients in Europe had more multiple lesions (23% vs 2%, P < .001), less invasive carcinoma (42% vs 85%, P < .001), and more intrahepatic tumors (52% vs 24%, P < .001) than in Nagoya. Patients in Europe experienced less 90-day grade >3 Clavien-Dindo complications (33% vs 68%, P < .001), but higher 90-day mortality rate (7.0% vs 0%, P = .03). R0 resections (81% vs 82%) were similar. Overall survival, excluding 90-day postoperative deaths, was similar in both regions. DiscussionDespite performing more extensive resections, the low perioperative mortality rate observed in Nagoya was probably influenced by a combination of patient-, tumor-, and surgery-related factors.

Management of Vernal Keratoconjunctivitis in Children in the United Kingdom: A Review of the Literature and Current Best Practice Across Six Large United Kingdom Centers.

Vernal keratoconjunctivitis (VKC) is a form of ocular allergy primarily affecting children. Considered a rare disease in Europe, its prevalence varies by geographic region and is poorly studied in the United Kingdom. There is considerable national variation in the management of VKC within the United Kingdom, risking misdiagnosis and delays to treatment for some children. This can significantly impact their quality of life, with the potential for lasting negative consequences. Based on discussions between experienced clinicians from six large centers across the United Kingdom, this article describes best practice recommendations for United Kingdom settings, including principles for diagnosis, referral, initial and long-term management, and supportive care. Recommendations include guidance on referral timing, which should depend on VKC severity, and a stepwise approach to treatment. Joint management by primary care and secondary care is recommended and the importance of supportive care, including emotional support and outreach to schools, is highlighted. Because frequent flareups are common in VKC, it is essential that families have access to the information they need to manage the disease and routes to access rapid care if needed. A thorough understanding of the nature of VKC, its triggers, and how best to manage it, by both patients and their families, is critical to ensuring appropriate management and to improving patient outcomes. [J Pediatr Ophthalmol Strabismus. 2023;60(1):6-17.].

Epidemiology of human alveolar echinococcosis in Armenia

Abstract Background Since the 90s' E.multilocularis infection in foxes is rising and central-eastern European countries had seen first Alveolar echinococcosis (AE) human cases. AE is considered to be a very rare disease in Europe with average incidences of 0.03-0.20/100,000 inhabitants/year. Because of a suitable orography, this study aims to confirm whether there are human AE cases in Armenia, identify areas at risk, and also estimate AE annual incidence. Methods Retrospective AE case finding was carried out at main 6 multi-profile medical centers equipped with the most innovative diagnostic means. The medical records of all patients with liver surgery admitted between January 2008 and June 2020 were reviewed. A specific form was developed in EpiInfo v. 7.2. Annual national incidence was estimated using population denominators provided by the National Institute of Statistics (the population of Armenia is estimated at 2 963 243 people). Results From September 2019 until June 2020, overall 11 AE cases have been identified. All patients were diagnosed at advanced stages, with subsequent poor prognosis and costly treatment. Confirmation was based on tissue biopsy results. Age ranged from 19-59 years with a median of 39yrs. E. multilocularis was detected in rural communities, mostly in the Gegharkunik region (6 cases, 55%). Annual average incidence of AE was 0.033 varying between 0.032 in 2008 and 0.1 in 2017. For comparison with Armenia, an annual incidence in France was 0.026/100,000 in 2008 (the population of France is estimated at 65 273 511 people). Conclusions All cases were not notified by the surveillance system and the real prevalence of AE in the country is unknown. This young age could indicate widespread of infection in animals. Therefore, the burden of AE disease is difficult to estimate. The surveillance system in Armenia can be improved by the development of national guidelines for the prospective registry, AE awareness campaigns. Key messages First-time identification of human AE in Armenia calls for implementation of surveillance with a case definition and registry of all cases. AE is an emerging, and so far silent threat in Armenia.

Development of a Dashboard for Rare Diseases - A Technical Case Report.

About 30 million people suffer from a rare disease in Europe. Those affected face a variety of problems. These include the lack of information and difficult access to scientific knowledge for physicians. For a higher visibility of rare diseases and high-quality research, effective documentation and use of data are essential. The aim of this work is to optimize the processing, use and accessibility of data on rare diseases and thus increase the added value from existing information. While dashboards are already being used to visualize clinical data, it is unclear what requirements are prevalent for rare diseases and how these can be implemented with available development tools so that a highly accepted dashboard can be designed. For this purpose, based on an analysis of the current situation and a requirements analysis, a prototype dashboard for the visualization of up-to-date key figures on rare diseases was developed at the University Hospital Carl Gustav Carus in Dresden. The development was based on the user-centered design process in order to achieve a high-level user-friendliness. The requirements analysis identified parameters that stakeholders wanted to see, focusing primarily on statistical analyses. The dashboard handles the automated calculation of statistics as well as their preparation and provision. The evaluations showed the prototypical dashboard would be considered valuable and used by potential users. This work demonstrates that stakeholders are interested in access to prepared information and exemplifies a way to implement it. The dashboard can increase the usage of existing information in terms of a higher accessibility and thus improve the knowledge about rare diseases.

Behçet's Disease in a Polish Patient: A Case Report.

Behçet’s disease (BD) is a systemic autoinflammatory vasculitis. It occurs predominantly in Turkey but very rarely in Europe. The clinical manifestations of BD involve the skin and mucosal membranes; cardiovascular, gastrointestinal and nervous systems; and the eyes and joints. A 26-year-old man was repeatedly hospitalized at the Department of Dermatology of the Medical University of Bialystok. He had a family history of family members' deaths from unknown cause and a long personal history of recurring headaches and nonspecific pain in the chest as well as a 2-year history of recurring painful erosions on the oral mucosa. Recently, before admission to hospital, another erosion had appeared on the scrotum, which rapidly evolved into a painful ulceration. The patient also presented a large erosion in the area of the right hip and acne lesions. He consulted doctors of different specialties and underwent laboratory and imaging tests. Considering the symptoms, BD was diagnosed. Azathioprine was introduced, along with topical treatment. Great improvement of the skin lesions was achieved. He was later admitted to the department a few times for follow-up visits and remains in good general condition. BD is an extremely rare disease in Europe, especially in Poland. The fact that BD is a rare disease outside Asia leads to lower awareness and the possibility of not considering it in the differential diagnosis. The great diversity of symptoms also causes difficulties in tracking this disease. The various manifestations of BD require a broad spectrum of additional tests and an interdisciplinary approach to the patient.

Bovine Babesiosis Diagnosed in Formalin-Fixed, Paraffin-Embedded Tissues by Using In Situ Hybridization.

Bovine babesiosis, caused by Babesia divergens, is in general a rare disease in Europe. Nonetheless, local outbreaks can cause severe economic damage, and postmortem identification represents a diagnostic challenge. During a recent outbreak in May 2018 in northern Germany, 21 animals of a herd of 150 cattle died within 40 days having had clinical signs of fever and hemoglobinuria. Gross examination of 4 of the 21 deceased animals revealed a tick infestation, jaundice, and dark brown staining of urine and kidneys. Histologically, there were iron-positive deposits, hyperplasia of the red pulp of the spleen, and centrilobular necrosis of hepatocytes. In several locations, small basophilic granules suggestive of intraerythrocytic parasites were visible in hematoxylin-eosin- and Giemsa-stained sections. Peripheral blood smears from a living cow from the herd and polymerase chain reaction (PCR) of feeding ticks revealed B. divergens infection. In situ hybridization (ISH) was applied on formalin-fixed, paraffin-embedded (FFPE) tissue of the necropsied cattle to confirm babesiosis in these animals postmortem. Digoxigenin-labeled DNA probes were generated based on a specific nucleotide sequence for B. divergens, obtained by PCR and sequencing of DNA isolates from infected Ixodes ricinus ticks from deceased cattle. ISH using these probes allowed postmortem diagnosis of B. divergens infection in routinely fixed FFPE tissues.

Chronic pulmonary histoplasmosis in Portugal: a case report

Pulmonary histoplasmosis is a rare disease in Europe caused by Histoplasma capsulatum, a dimorphic fungus present in the soil contaminated with excrements of birds and bats. There are two varieties, variety capsulatum endemic of American continent and variety duboisii endemic of African continent. All cases in Europe were imported. In this article, we present a case of chronic pulmonary histoplasmosis, a rare presentation of histoplasmosis in an immunocompetent man several years after he has lived in a endemic region of Africa. He complained of fatigue and dyspnea in the last two years. In computed tomography of the chest, it was verified multiple and bilateral focus of densification with peribronchovascular distribution. Transthoracic lung biopsy was then requested, whose pathological anatomy revealed epithelioid granulomas infected by yeast from Histoplasma capsulatum.

Penile cancer – Incidence, mortality, and survival in Saxony, Germany

ObjectivePenile cancer is a rare disease in Europe and North America. Cancer registry data were used to estimate the incidence, mortality, and survival of penile cancer in Saxony, Germany. MethodsData on incidence were analyzed for the period 1961 to 2012 and mortality for the period 1990 to 2012. Trend analyses of incidence and mortality were performed using joinpoint regression. Survival rates for primary penile cancer (ICD-10 C60) were estimated; overall, by T stage, UICC stage, and by year of diagnosis for the years 1963 to 2012. ResultsAge-standardized incidence increased from 1.2 per 100,000 in 1961 to 1.8 per 100,000 in 2012, with a statistically significant increase between 2003 and 2012 (annual percent change: 4.66; 95% confidence interval, CI 0.62–8.86). There was a statistically significant negative trend in mortality between 1990 and 2012 (annual percent change: −3.46, 95% CI −5.21 to −1.67). A total of 430 new cases of penile cancer were registered between 2003 and 2012, with 63% of all penile cancers occurring in men aged 60 to 79 years. Almost half of those cases were located at the glans penis. The overall relative 5-year survival for the years of diagnosis 2003 to 2012 was 72.4% (95% CI 64.8%–80.0%). Relative 5-year survival decreased with higher UICC stages (I: 96%, 95% CI 84.7%–107.3%; II: 86.3%, 95% CI 71.0%–101.5%; III: 39.6%, 95% CI 19.9%–59.3%; IV: 20.3%, 95% CI 2.4%–38.2%). ConclusionThe incidence of penile cancer in Saxony has increased in recent years, while mortality has decreased. However, survival rates have remained constant over time.

What Happens after Kasai for Biliary Atresia? A European Multicenter Survey.

Biliary atresia (BA) remains a rare disease in Europe with an estimated incidence of 1 in 15-20,000 livebirths. While the Kasai portoenterostomy (KPE) is regarded as the standard operation for BA, there is no consensus on optimum adjuvant therapy. We sought to determine the variation in therapy and opinion in centers known to have an interest in pediatric hepatobiliary surgery across Europe. A survey of current pre- and postoperative practice was circulated to surgeons and centers known to have an interest in BA. Data are quoted as median (range). There were 19 completed center forms from 12 different countries. Annual (new) caseload varied with 10 centers reported seeing ≤5 patients/year and 4 centers >15 patients/year. The distribution of BA variants was isolated BA (80 [60-100]%), syndromic BA (10 [3-35]%), cystic BA (5 [1-15]%), and cytomegalovirus (CMV) immunoglobulin M (IgM)-positive BA (5 [0-15]% (CMV serology only formally tested in 16 centers). The commonest age group at KPE was 51 to 60 days (n = 8). All centers performed an exclusively open KPE, although one used laparoscopy for diagnosis. A steroid-based postoperative regimen was used in 11/19 (58%) centers, but with marked variation in dose and duration. Commonest perioperative antibiotics were a combination of piperacillin-tazocin (n = 7) and gentamicin (n = 8). Oral prophylactic antibiotics, with varying duration (4-52 weeks) were used in 13/19 (68%) centers. If CMV serology was positive, seven centers would treat with specific antiviral therapy. Other postoperative medication included ursodeoxycholic acid (UDCA) (n = 19), phenobarbitone (n = 4), and cholestyramine (n = 2). Self-declared clearance of jaundice in centers varied from 30 to 40% (n = 3) to > 60% (n = 5). All surveyed European centers continue to perform an exclusively open KPE, but there is no consensus on a standard adjuvant drug regimen. Self-declared outcome post-KPE also appears to be variable though the reasons are obscure.

Penetrating Limbokeratoplasty for Gelatinous Corneal Dystrophy

Gelatinous corneal dystrophy is a very rare disease in Europe and North America. Patients suffer from pain, photophobia and loss of vision, usually before the age of 20. Transplantation of limbal stem cells was proposed due to the high rate of recurrence after conventional penetrating keratoplasty. We present the results of penetrating limbokeratoplasty, a combined transplantation of cornea and limbal stem cells, in patients with gelatinous corneal dystrophy. We present a series of 7 consecutive eyes with gelatinous corneal dystrophy, which were treated with penetrating limbokeratoplasty-4 eyes of 3 patients had already undergone multiple conventional corneal transplantations. We evaluated the follow-up regarding recurrences of the disease, graft rejections, clear graft survival and incidence of secondary glaucoma with the Kaplan-Meier method. Median age at surgery was 35 years. Postoperative treatment included topical steroids and systemic mycophenolate mofetil in all patients. Median graft survival was 6 years. Median time to a recurrence was 3 years. Median time to the first endothelial graft rejection was 2.5 years. Penetrating limbokeratoplasty offers a possibility to restore visual acuity over a long period of time. However, gelatinous corneal dystrophy remains a therapeutic challenge. Even with simultaneous transplantation of cornea and limbal stem cells, recurrences of the disease cannot be prevented permanently. This is also connected with discontinuing a sufficient local and systemic immunosuppression.

Graves\u2019 orbitopathy as a rare disease in Europe: a European Group on Graves\u2019 Orbitopathy (EUGOGO) position statement

BackgroundGraves’ orbitopathy (GO) is an autoimmune condition, which is associated with poor clinical outcomes including impaired quality of life and socio-economic status. Current evidence suggests that the incidence of GO in Europe may be declining, however data on the prevalence of this disease are sparse. Several clinical variants of GO exist, including euthyroid GO, recently listed as a rare disease in Europe (ORPHA466682).The objective was to estimate the prevalence of GO and its clinical variants in Europe, based on available literature, and to consider whether they may potentially qualify as rare. Recent published data on the incidence of GO and Graves’ hyperthyroidism in Europe were used to estimate the prevalence of GO. The position statement was developed by a series of reviews of drafts and electronic discussions by members of the European Group on Graves’ Orbitopathy. The prevalence of GO in Europe is about 10/10,000 persons. The prevalence of other clinical variants is also low: hypothyroid GO 0.02–1.10/10,000; GO associated with dermopathy 0.15/10,000; GO associated with acropachy 0.03/10,000; asymmetrical GO 1.00–5.00/10,000; unilateral GO 0.50–1.50/10,000.ConclusionGO has a prevalence that is clearly above the threshold for rarity in Europe. However, each of its clinical variants have a low prevalence and could potentially qualify for being considered as a rare condition, providing that future research establishes that they have a distinct pathophysiology. EUGOGO considers this area of academic activity a priority.

8th European Conference on Rare Diseases &amp; Orphan Products (ECRD 2016)

Table of contentsO1 The European Social Preferences Measurement (ESPM) study project: social cost value analysis, budget impact, commercial life cycle revenue management, and the economics of biopharmaceutical Research & Development (R&D)Michael Schlander, Søren Holm, Erik Nord, Jeff Richardson, Silvio Garattini, Peter Kolominsky-Rabas, Deborah Marshall, Ulf Persson, Maarten Postma, Steven Simoens, Oriol de Solà Morales, Keith Tolley, Mondher Toumi, Harry TelserO2 Newborn Screening: the potential and the challengesJames R BonhamO3 Untreatable disease outcomes - how would we measure them?Helmut Hintner, Anja Diem, Martin LaimerO4 Taking Integrated Care Forward: Experiences from Canada to inspire service provision for people living with rare disease in EuropeRéjean HébertO5 Listening to the patient’s voice: social media listening for safety and benefits in rare diseasesNabarun Dasgupta, Carrie E. Pierce, Melissa JordanO6 Via Opta: Mobile apps making visually impaired patients’ lives easier Barbara Bori, Mohanad Fors, Emilie PrazakovaO7 A report of the IRDiRC “Small Population Clinical Trial” Task ForceSimon DayO8 HAE patient identification and diagnosis: An innovative, ‘game changing’ collaborationThomas J. Croce Jr.O9 Co-creating with the community: primary packaging & administration for people with haemophiliaJonas Fransson, Philip WoodO10 Go with Gaucher, taking forward the next generation. How to involve young people to create a new generation of patient advocatesAnne-Grethe Lauridsen, Joanne Higgs, Vesna Stojmirova AleksovskaP1 ODAK – Orphan Drug for Acanthamoeba KeratitisChristina Olsen, Ritchie Head, Antonio Asero, Vincenzo Papa, Christa van Kan, Loic Favennec, Silvana Venturella, Michela Salvador, Alan KrolP5 Rare Navigators help people living with rare diseases to manage the social – and healthcare systems Stephanie J. Nielsen, Birthe B. HolmP6 The eAcademy for Tay-Sachs & Sandhoff disease appDaniel Lewi, Patricia DurãoP10 The role of a patient organisation in driving the research agenda in a rare diseaseHeather Band, Andrea WestP13 Expertise for rare diseases mappedMarinda J.A. Hammann, Marije C. Effing-Boele, Hanka K. DekkerP14 The hidden costs of rare diseases: a feasibility studyAmy Hunter, Amy SimpsonP15 FDA’s new natural history grant program: support to build a solid foundation for development of products for rare diseasesGumei Liu, Katherine Needleman, Debra Lewis, Gayatri RaoP17 Understanding the wider impact of adrenal insufficiency: patient organisation involvement in the TAIN projectAmy Simpson, Amy Hunter, Martin J WhitakerP20 Bridging the gaps between medical and social care for people living with a rare diseaseRaquel Castro

Echinococcus multilocularis: Epidemiology, surveillance and state-of-the-art diagnostics from a veterinary public health perspective

Alveolar echinococcosis (AE), caused by the larval (metacestode) stage of Echinococcus multilocularis, is considered one of the most serious parasitic zoonoses in Central and Eastern Europe and is emerging also in large parts of Asia and in North America. The red fox represents the main definitive host of E. multilocularis in Europe, but the raccoon dog, the domestic dog and to a much lesser extent the domestic cat also represent potential definitive hosts. The natural intermediate hosts of E. multilocularis are mainly voles. The spectrum of accidental hosts is broad and includes many species of monkeys, pigs, dogs and humans which get infected by oral uptake of the viable eggs. Yet, human AE is a very rare disease in Europe; incidences have increased in recent years, while the infection is widely distributed in foxes with high prevalences reaching up to 70% in some areas. Generally, infected foxes represent a zoonotic risk, which may be particularly relevant in urban areas. Furthermore, there is concern that the risk for humans to acquire AE may rise due to the suspected geographical spread of the parasite as assessed by infections in its definitive hosts and the high prevalences in some regions. Monitoring and surveillance activities have therefore been initiated in a few European countries. Several diagnostic strategies have been developed and validated in recent years, applying classical worm detection by microscopy, but also immunological (ELISA for coproantigen detection) and molecular tests (copro-DNA detection by PCR). However, there is an urgent need for defining minimal requirements and harmonised approaches for these activities to allow for a reliable assessment of the epidemiological situation in Europe and comparable results from different countries.

'Time-to-amphotericin B' in cryptococcal meningitis in a European low-prevalence setting: analysis of diagnostic delays.

Cryptococcal meningitis is a rare disease in Europe, resulting in delayed recognition and slower initiation of specific treatment. To analyse the time-to-treatment and the factors that delay the diagnosis and treatment in the low-prevalence setting of a European centre. Retrospective review We reviewed full medical records of all adult patients with cryptococcal meningitis referred to an HIV centre in Berlin, Germany in 10-year period between 1st of October 2003 and 31st of September 2013. Multivariant statistics with bootstrap-resampling were performed. We identified 19 patients with a diagnosis of HIV-related cryptococcal meningitis (0.55% of all consecutive HIV-infected patients). In almost half of our patients the diagnosis was not considered initially on admission to the secondary care centre and the first diagnostic clue being an accidental positive blood, cerebrospinal fluid or bronchoalveolar lavage culture growing Cryptococcus neoformans. The median time-to-treatment was 5 days (range: 1-16). Known positive HIV status accelerated the time-to-diagnosis (p < 0.05) by a median of 1.89 days, whereas the CSF cell count ≤ 10/µl delayed diagnosis by a median time of 1.93 days (p < 0.1). Diagnostic delays could be avoided by encouraging practising physicians (i) to consider cryptococcal meningitis in immunosuppressed HIV-infected patients irrespective of neurological symptoms; (ii) to test for India ink, cryptococcal antigen and fungal cultures in immunosuppressed HIV-infected patients with normal CSF; (iii) to consider a possibility of underlying HIV infection in patients with unknown HIV status presenting with meningitis; and (iv) to consider early targeted HIV testing in persons at risk according to locally validated criteria.

NK/T-Zell-Lymphom vom nasalen Typ mit kutaner Dissemination

Extranodal NK/T-cell lymphoma, nasal type, is a lymphoproliferative disorder originating from peripheral T-cells or natural killer (NK) cells. While it is a rare disease in Europe, it is more frequent in Asia and South America. It is associated with Epstein-Barr virus (EBV) infection and characterized by an extremely aggressive course and poor prognosis. We report a 46-year-old Caucasian woman who presented with multiple subcutaneous, painful nodules on the trunk first noticed a few weeks earlier. In addition to dermatological findings, the patient reported a 4-months history of necrotizing nasopharyngeal inflammation of unclear origin. Due to nonspecific histological and clinical findings mimicking a chronic inflammatory condition, a diagnosis of Wegener disease was made and immunosuppressive therapy with azathioprine was initiated. However the disease progressed under therapy. Histopathological reevaluation and immunophenotyping revealed a disseminated NK/T-cell lymphoma, nasal type. In the case of an unspecific chronic inflammatory process in the nasopharyngeal space one should always consider the possibility of this rare lymphoma, even in Europe.

Distinct Host Species Correlate with Anaplasma phagocytophilum ankA Gene Clusters

Anaplasma phagocytophilum is a gram-negative, tick-transmitted, obligate intracellular bacterium that elicits acute febrile diseases in humans and domestic animals. In contrast to the United States, human granulocytic anaplasmosis seems to be a rare disease in Europe despite the initial recognition of A. phagocytophilum as the causative agent of tick-borne fever in European sheep and cattle. Considerable strain variation has been suggested to occur within this species, because isolates from humans and animals differed in their pathogenicity for heterologous hosts. In order to explain host preference and epidemiological diversity, molecular characterization of A. phagocytophilum strains has been undertaken. Most often the 16S rRNA gene was used, but it might be not informative enough to delineate distinct genotypes of A. phagocytophilum. Previously, we have shown that A. phagocytophilum strains infecting Ixodes ricinus ticks are highly diverse in their ankA genes. Therefore, we sequenced the 16S rRNA and ankA genes of 194 A. phagocytophilum strains from humans and several animal species. Whereas the phylogenetic analysis using 16S rRNA gene sequences was not meaningful, we showed that distinct host species correlate with A. phagocytophilum ankA gene clusters.

Recommendations for the development of national plans for rare diseases

Rare diseases are a threat to the health of EU citizens, in so far as they are life-threatening or chronically debilitating diseases with a low prevalence and a high level of complexity. Despite their rarity, there are so many different types of rare diseases that millions of people are affected. The focus on rare diseases and the recognition of the fact that rare diseases have common issues in a public health perspective and require specifically targeted policies, is a relatively new achievement in most EU member states. There is at present great variability among countries about the type of services provided to rare disease patients and the accessibility to these services. Following the Council Recommendations, each Member State should (preferably by the end of 2013) establish and implement plans or strategies for rare diseases at the appropriate level. The aim is to ensure that all patients with a rare disease in Europe have equal access to high-quality care, including diagnostics, treatments and rehabilitation. The European Project for Rare Diseases National Plans Development (EUROPLAN), has the task of elaborating documents to facilitate the establishment and implementation of National Plans or Strategies. EUROPLAN has defined a National Plan or Strategy as a set of integrated and comprehensive health and social policy actions for rare diseases, to be developed and implemented at national level, and characterised by identified objectives to be achieved within a specified timeframe. The EUROPLAN guidance document (recommendations) provides a set of “tools and examples” on how activities for rare diseases can be organised at national (and European) level on different areas, e.g. the coding (and traceability) of rare diseases, research, centres of expertise and the empowerment of patient organisations for rare diseases. (http://www.europlanproject.eu)

Primary Tuberculosis of the Cheek skin: Difficulties in Diagnostic Procedure

Background. Tuberculosis of the skin is rare disease in Europe. Diagnostic procedure is long and difficult. Aim. Aim of our manuscript is to point out that in differential diagnosis of chronic skin diseases, it is necessary to take tuberculosis into consideration as well. We represented rare case of cutaneous tuberculosis that required surgical procedure. Case report. A 46-year-old female, psychiatric patient, was referred to our clinic on surgical treatment of buccal abscess on the cheek. We extracted the teeth that were considered to be cause of inflammation, and the anthibiotic therapy was prescribed. Patient was seen after nearly two months. At the place of previous skin incision there was a visible fissure with surrounding erythematic and desquamation, and the fistula on the buccal mucous membrane. The findings of probatory biopsy showed elements of granulomatous inflammation. The first findings for Mycobacterium tuberculosis were negative. However, after five weeks the cultivation test was positive. The focus of infection was not found anywhere else.

The rare diseases agenda of the European Parliament

During the past years, rare diseases have been one of the main themes on the European Union’s agenda. The reason for this theme being highlighted is the excellent exchange of knowledge between EU policy makers and the relevant patient communities. The former negligence has been caused by the apparent low patient numbers. The definition of a rare disease in Europe contains, that there are less than five patients out of a total population of 10000 persons suffering from this disease. Taking the total of all patients, suffering from rare diseases, it becomes a different number. An estimated 30 million EU citizens are suffering from a rare disease. This tells us that rare diseases are actually not exactly rare. Due to the great part of the population,which is affected, we have a social obligation to prioritise on this matter. Furthermore, the type of health conditions deserves a strong focus. The European Union, and notably the European Parliament, has made significant progress towards the provision of a political framework, which would define rare diseases and provide incentives for the research and development of medicines. The EU Orphan Medicines Regulation, adopted in 1999, was a political milestone in the prioritisation of rare diseases. It has provided the European Union with a clear competence in refining this topic. It was this legislation, which created incentives for medical manufacturers to develop products, furthermore, they generated a market exclusivity going beyond patent protection and a fee waiver for the evaluation and registration process of specialized products. The establishment of the European Medicines Evaluation Agency (EMEA) in 1995, meant the foundation of a centralised body, which can appropriately deal with the necessary central registration of available and registered medicines. This has been a great success story. Since then, 639 products have been registered with the European Medicines Agency. More importantly, the Agency transformed Europe to a leading region for research and development in this field.