How the EUCERD Joint Action supported initiatives on Rare Diseases.

Eur J Med Genet. 2017 Mar;60(3):185-189

Authors: Lynn S, Hedley V, Atalaia A, Evangelista T, Bushby K, EUCERD Joint Action

Abstract
Joint Actions are successful initiatives from the European Commission (EC) that have helped to raise awareness and to bring significant benefit to those suffering from a rare disease (RD). In this paper, we will focus on the activities developed by the EUCERD Joint Action (EJA) and by the Orphanet Joint Action ("Orphanet Europe"). EUCERD Joint Action was co-funded by the EC and the Member States between 2012 and 2015 to help to define the activities and policies in the field of RD and foster exchange of experiences amongst Member States. This project is the continuation of previous efforts to turn RD a priority in the EC Health Programmes. "Orphanet Europe" was a Joint Action co-funded by INSERM, the French Directorate General for Health and the EC to address the need for a common portal that would gather the most update information regarding RD. This need was identified in the European Commission report "Rare Diseases: Europe's challenge" and in the Recommendation of the Council for a European RD portal. These joint actions have supported the policy development work of the European Commission, through the support of their committees for rare diseases. In this paper, the authors aim to raise awareness of the work done by the EUCERD Joint Action on behalf of the rare disease community and the policies established.

PMID: 28087401 [PubMed - indexed for MEDLINE]

Subcorneal Pustular Dermatosis: A Review of 30 Years of Progress.

Am J Clin Dermatol. 2016 Dec;17(6):653-671

Authors: Watts PJ, Khachemoune A

Abstract
Subcorneal pustular dermatosis (SPD), also known as Sneddon-Wilkinson disease, is a rare, benign yet relapsing pustular dermatosis. Its incidence and prevalence have not been well studied. It characteristically presents as hypopyon pustules on the trunk and intertriginous areas of the body. SPD is similar to two other disease entities. Both SPD-type immunoglobulin (Ig)-A pemphigus and annular pustular psoriasis clinically and histologically present similarly to SPD. Immunologic studies separate SPD-type IgA pemphigus from SPD and pustular psoriasis. However, there is still an unclear designation as to whether SPD is its own entity distinct from pustular psoriasis, as the once thought characteristic histologic picture of psoriasis does not hold true for pustular psoriasis. SPD has been reported to occur in association with several neoplastic, immunologic, and inflammatory conditions. Dapsone remains the first-line treatment for SPD, although dapsone-resistant cases have been increasingly reported. Other therapies have been used singly or as adjunctive therapy with success, such as corticosteroids, immunosuppressive agents, tumor necrosis factor inhibitors, and ultraviolet light therapy. This article provides a review of the last 30 years of available literature, with a focus on successful treatment options and a suggestion for reappraisal of the classification of SPD.

PMID: 27349653 [PubMed - indexed for MEDLINE]

Parent Recommendations for Family Functioning With Prader-Willi Syndrome: A Rare Genetic Cause of Childhood Obesity.

J Pediatr Nurs. 2016 Jan-Feb;31(1):47-54

Authors: Vitale SA

Abstract
UNLABELLED: Prader-Willi syndrome (PWS) is the most common genetic cause of childhood obesity. Neonates have hypotonia and may fail to growth and develop. Within a few years, behavioral problems occur along with insatiable hunger (hyperphagia) and the potential for excessive weight gain. The purpose of this study was to identify how families function when they have a child with PWS.
DESIGN AND METHODS: This qualitative descriptive study was based on 20 face-to-face, audio-taped interviews with parents. They were asked to identify family responses to PWS and offer recommendations. Data were transcribed, coded and analyzed for commonalities and themes.
RESULTS: There were twelve identified themes with two overarching themes of 1) taking action and 2) caring for oneself and family. Taking action was focused on achieving what was best for the child with PWS. Caring for oneself and family attempted to assure that all in the family were healthy, content, and living a fulfilling life under their circumstances.
CONCLUSIONS: This study revealed parental insight as to how they learned to creatively cope with a stressful family life. There was a recognition of inevitable sacrifice and the need for changes in expectations so as to help the child with PWS flourish while also focusing on the needs of all the members of the family.
PRACTICE IMPLICATIONS: Nursing and health care providers should be aware of these issues in the provision of anticipatory guidance to families contending with this genetic disorder.

PMID: 26684080 [PubMed - indexed for MEDLINE]

A review and update on orphan drugs for the treatment of noninfectious uveitis.

Clin Ophthalmol. 2017;11:257-265

Authors: You C, Sahawneh HF, Ma L, Kubaisi B, Schmidt A, Foster CS

Abstract
INTRODUCTION: Uveitis, a leading cause of preventable blindness around the world, is a critically underserved disease in regard to the medications approved for use. Multiple immunomodulatory therapy (IMT) drugs are appropriate for uveitis therapy but are still off-label. These IMT agents, including antimetabolites, calcineurin inhibitors, alkylating agents, and biologic agents, have been designated as "orphan drugs" and are widely used for systemic autoimmune diseases or organ transplantation.
AREA COVERED: The purpose of this paper is to comprehensively review and summarize the approved orphan drugs and biologics that are being used to treat systemic diseases and to discuss drugs that have not yet received approval as an "orphan drug for treating uveitis" by the US Food and Drug Administration (FDA).
OUR PERSPECTIVE: IMT, as a steroid-sparing agent for uveitis patients, has shown promising clinical results. Refractory and recurrent uveitis requires combination IMT agents. IMT is continued for a period of 2 years while the patient is in remission before considering tapering medication. Our current goals include developing further assessments regarding the efficacy, optimal dose, and safety in efforts to achieve FDA approval for "on-label" use of current IMT agents and biologics more quickly and to facilitate insurance coverage and expand access to the products for this orphan disease.

PMID: 28203051 [PubMed - in process]

A 36-Year-Old Female with Recurrent Left Sided Pleural Effusion: A Rare Case of Mediastinal Lymphangioma.

Am J Case Rep. 2016 Oct 28;17:799-804

Authors: Swarnakar RN, Hazarey JD, Dhoble C, Vaghani B, Ainsley AS, Khargie JF, Likaj L

Abstract
BACKGROUND Lymphangioma is an atypical non-malignant, lymphatic lesion that is congenital in origin. Lymphangioma is most frequently observed in the head and neck, but can occur at any location in the body. About 65% of lymphangiomas are apparent at birth, while 80-90% are diagnosed by two years of age. Occurrence in adults is rare, as evidenced by less than 100 cases of adult lymphangiomas reported in the literature. CASE REPORT A 36-year-old Indian woman with a medical history of recurrent pleural effusions presented with chief complaints of dyspnea on exertion for one year and a low-grade fever for one month. A thorax CT revealed left-sided pleural effusion with thin internal septations. Thoracoscopy revealed a large cystic lesion arising from the mediastinum from the hilum surrounding the mediastinal great vessels. The diagnosis of lymphangioma was confirmed via histopathologic examination of the cyst. It was managed with partial cystectomy along with the use of a sclerosing agent (talc). CONCLUSIONS The size and location of lymphangiomas can vary, with some patients presenting with serious problems like respiratory distress, while others may be asymptomatic. Complete cyst resection is the gold standard treatment for mediastinal cystic lymphangioma. Partial cyst resection along with the use of sclerosing agents can be an effective option when complete cystectomy is not possible. Although lymphangioma is a rare patient condition, it should be included in the differentials for patients presenting with pleural effusions. Also, a biopsy should be done at the earliest opportunity to differentiate lymphangioma from other mediastinal malignant tumors.

PMID: 27789902 [PubMed - indexed for MEDLINE]

Integrated multidisciplinary care for the management of chronic conditions in adults: an overview of reviews and an example of using indirect evidence to inform clinical practice recommendations in the field of rare diseases.

Haemophilia. 2016 Jul;22 Suppl 3:41-50

Authors: Yeung CH, Santesso N, Zeraatkar D, Wang A, Pai M, Sholzberg M, Schünemann HJ, Iorio A

Abstract
BACKGROUND: Integrated care models have been adopted for individuals with chronic conditions and for persons with rare diseases, such as haemophilia.
OBJECTIVE: To summarize the evidence from reviews for the effects of integrated multidisciplinary care for chronic conditions in adults and to provide an example of using this evidence to make recommendations for haemophilia care.
SEARCH METHODS: We searched MEDLINE, EMBASE, CINAHL and Cochrane Database of Systematic Reviews up to January 2016, and reviewed reference lists of retrieved papers.
SELECTION CRITERIA: Systematic reviews of at least one randomized study, on adults with non-communicable chronic conditions.
DATA COLLECTION AND ANALYSIS: Two investigators independently assessed eligibility and extracted data. Quality of reviews was assessed using ROBIS, and the evidence assessed using GRADE.
RESULTS: We included seven reviews reporting on three chronic conditions. We found low to high quality evidence. Integrated care results in a reduction in mortality; likely a reduction in emergency visits and an improvement in function; little to no difference in quality of life, but shorter hospital stays; and may result in little to no difference in missed days of school or work. No studies reported educational attainment, or patient adherence and knowledge. When used for haemophilia, judgment about the indirectness of the evidence was driven by disease, intervention or outcome characteristics.
CONCLUSION: This overview provides the most up to date evidence on integrated multidisciplinary care for chronic conditions in adults, and an example of how it can be used for guidelines in rare diseases.

PMID: 27348400 [PubMed - indexed for MEDLINE]

Giant cell tumours in fingers among the Inuit population in Greenland.

Int J Circumpolar Health. 2016;75:31285

Authors: Duelund N, Hougaard K

Abstract
OBJECTIVE: Giant cell tumours (GCTs) of the tendon sheets in fingers are rare. We therefore find it of interest to report on 5 cases identified in the Inuit population in Greenland within 16 months prior to this study.
MATERIAL AND METHODS: The Inuit account for 56,000 people of the total population in Greenland. From November 2010 to 16 months prior to this study, we diagnosed 5 cases (0.6% of all orthopaedic operations) with a GCT of the flexor tendon sheet of a finger. The patients were aged between 10 and 54 years, and 4 were women. All of them had noticed slow-growing tumours over 3 or more years and were referred for a suspected ganglion.
RESULTS: In two cases, the tumour was located at the distal interphalangeal (DIP) joint in the thumb and in one case at the third finger. Two other patients had tumours at the metacarpophalangeal (MCP) joint of the third finger and the thumb, respectively; one of these two had a communicating tumour to the DIP joint. The last patient had two tumours on the same finger, one at the MCP joint and the other at the DIP joint. In one case, the tumour had also eroded the cortex of the first phalanx of the thumb, and the largest tumour measured 5 cm.
CONCLUSION: GCTs of the flexor tendon sheets in fingers are rare. It could be a coincidence that we have seen 5 cases within a short period of time. It is not possible to identify past cases through a register. A tumour in a finger is not the most common location for a ganglion, especially not at the DIP level. Therefore, a large tumour at this location is more likely to be a GCT.

PMID: 27052154 [PubMed - indexed for MEDLINE]

7 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"Rare Diseases"[Mesh] OR "orphan disease"

These pubmed results were generated on 2017/02/16

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

6 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"Rare Diseases"[Mesh] OR "orphan disease"

These pubmed results were generated on 2017/02/15

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

The Pediatric Research Equity Act Moves Into Adolescence.

JAMA. 2017 01 17;317(3):259-260

Authors: Bourgeois FT, Hwang TJ

PMID: 28114560 [PubMed - indexed for MEDLINE]

[Urothelial tumors in children].

Bull Cancer. 2017 Feb;104(2):195-201

Authors: Grapin-Dagorno C, Peycelon M, Philippe-Chomette P, Berrebi D, El Ghoneimi A, Orbach D

Abstract
Urothelial tumors are very rare in children (to date, only about 150 cases have been reported worlwide). Only 20% occur before the age of ten. The aim of this study is to specify the clinicopathologic features of urothelial tumor in young patients, which require a slightly different approach to treatment. On the basis of the WHO/ISUP (World Health Organisation/International Society of Urological Pathology) consensus classification report, these lesions are usually low-grade lesions, non invasive, and rarely recurrent. The sex ratio is three boys to one girl. These tumors are located preferentially in the low urinary tract, especially in the bladder. The main symptom is the macroscopic hematuria, which requires ultrasound examination in all cases. Cystoscopy is indicated in case of lesion of the bladder wall, or in case of persistent or recurrent hematuria, to obtain definitive diagnosis and biopsies. The tumors are mainly located on the posterior or lateral bladder wall above the trigone or near the ureteral orifices. Treatment is based on the transurethral resection of the lesion. The subsequent monitoring is sparsely codified, due to the exceptional occurrence of these tumors in the paediatric age group. These patients are likely to have better outcome than older patients, but it is due to the predominance of noninvasive papillary urothelial tumors. Tumor recurrences are not uncommon. In case of invasive, high-grade urothelial carcinomas, metastases or even lethal outcome may occur in rare cases.

PMID: 28034440 [PubMed - indexed for MEDLINE]

[Nasopharyngeal adenoid cystic carcinoma, a rare but highly challenging disease with unmet therapeutic needs: A case-report and review of the literature].

Cancer Radiother. 2016 Jul;20(5):400-4

Authors: Afani L, Errihani H, Benchafai I, Lalami Y

Abstract
Nasopharyngeal adenoid cystic carcinoma is a rare tumour. Compared with others nasopharyngeal tumours, it is characterised by slow evolution but it is locally aggressive and has a high tendency to recurrences. Due to the rarity of cases, no consensus exists about treatment approaches. We report the case of 45-year-old-man with a locally advanced adenoid cystic carcinoma. The patient received concurrent chemoradiation and had a good objective response. After one year, he developed a paucisymptomatic lung metastasis. The follow-up showed local recurrence after 3 years. One cycle of chemotherapy was given but poorly supported. Carbon ion radiotherapy was proposed. The aim of this work is to review the literature concerning this rare malignancy and discusses treatment approaches in initial situations and during recurrences.

PMID: 27131394 [PubMed - indexed for MEDLINE]

Encapsulating Peritoneal Sclerosis - Rare Cause Of Bowel Obstruction.

Pol Przegl Chir. 2015 Jul 01;87(7):371-4

Authors: Dec P, Józefowicz M, Lesińska A, Kubisa B

PMID: 26351794 [PubMed - indexed for MEDLINE]

6 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"Rare Diseases"[Mesh] OR "orphan disease"

These pubmed results were generated on 2017/02/12

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

Drug discovery for Diamond-Blackfan anemia using reprogrammed hematopoietic progenitors.

Sci Transl Med. 2017 Feb 08;9(376):

Authors: Doulatov S, Vo LT, Macari ER, Wahlster L, Kinney MA, Taylor AM, Barragan J, Gupta M, McGrath K, Lee HY, Humphries JM, DeVine A, Narla A, Alter BP, Beggs AH, Agarwal S, Ebert BL, Gazda HT, Lodish HF, Sieff CA, Schlaeger TM, Zon LI, Daley GQ

Abstract
Diamond-Blackfan anemia (DBA) is a congenital disorder characterized by the failure of erythroid progenitor differentiation, severely curtailing red blood cell production. Because many DBA patients fail to respond to corticosteroid therapy, there is considerable need for therapeutics for this disorder. Identifying therapeutics for DBA requires circumventing the paucity of primary patient blood stem and progenitor cells. To this end, we adopted a reprogramming strategy to generate expandable hematopoietic progenitor cells from induced pluripotent stem cells (iPSCs) from DBA patients. Reprogrammed DBA progenitors recapitulate defects in erythroid differentiation, which were rescued by gene complementation. Unbiased chemical screens identified SMER28, a small-molecule inducer of autophagy, which enhanced erythropoiesis in a range of in vitro and in vivo models of DBA. SMER28 acted through autophagy factor ATG5 to stimulate erythropoiesis and up-regulate expression of globin genes. These findings present an unbiased drug screen for hematological disease using iPSCs and identify autophagy as a therapeutic pathway in DBA.

PMID: 28179501 [PubMed - in process]

Turning the Unknown into Known: Data Mining Is Increasingly Used to Prospect for Rare-Disease Biology and Treatments.

IEEE Pulse. 2017 Jan-Feb;8(1):28-32

Authors: Mertz L

Abstract
Taken as a whole, rare diseases are not very rare. Even though a rare disease by definition is one that affects fewer than 200,000 Americans or fewer than one in 2,000 Europeans at any time, when rare diseases are considered together, they affect some 350 million people worldwide, or about 5% of the population (Figure 1). What is even more alarming is that 7,800 of the approximately 8,000 known rare diseases have no treatments available. It's not that rare diseases are harder to treat than more widespread illnesses. Rather, compared to more common disorders, rare diseases simply do not draw the same level of attention from granting agencies, pharmaceutical companies, medical professionals, and researchers, so they languish in the shadows.

PMID: 28129139 [PubMed - indexed for MEDLINE]

Case report of a Li-Fraumeni syndrome-like phenotype with a de novo mutation in CHEK2.

Medicine (Baltimore). 2016 Jul;95(29):e4251

Authors: Zhuang X, Li Y, Cao H, Wang T, Chen J, Liu J, Lin L, Ye R, Li X, Liu S, Li W, Lv Y, Zhang J, He C, Xu X, Wang Z, Huang C, Liu X, Wang L

Abstract
BACKGROUND: Cases of multiple tumors are rarely reported in China. In our study, a 57-year-old female patient had concurrent squamous cell carcinoma, mucoepidermoid carcinoma, brain cancer, bone cancer, and thyroid cancer, which has rarely been reported to date.
METHODS: To determine the relationship among these multiple cancers, available DNA samples from the thyroid, lung, and skin tumors and from normal thyroid tissue were sequenced using whole exome sequencing.
RESULTS: The notable discrepancies of somatic mutations among the 3 tumor tissues indicated that they arose independently, rather than metastasizing from 1 tumor. A novel deleterious germline mutation (chr22:29091846, G->A, p.H371Y) was identified in CHEK2, a Li-Fraumeni syndrome causal gene. Examining the status of this novel mutation in the patient's healthy siblings revealed its de novo origin.
CONCLUSION: Our study reports the first case of Li-Fraumeni syndrome-like in Chinese patients and demonstrates the important contribution of de novo mutations in this type of rare disease.

PMID: 27442652 [PubMed - indexed for MEDLINE]

Rare cardiovascular diseases: from European legislations to classification and clinical practice.

Kardiol Pol. 2015;73(3):135-41

Authors: Podolec P, Stępniewski J, Podolec J, Kopeć G

PMID: 25371302 [PubMed - indexed for MEDLINE]

Data quality in rare cancers registration: the report of the RARECARE data quality study.

Tumori. 2017 Jan 21;103(1):22-32

Authors: Trama A, Marcos-Gragera R, Sánchez Pérez MJ, van der Zwan JM, Ardanaz E, Bouchardy C, Melchor JM, Martinez C, Capocaccia R, Vicentini M, Siesling S, Gatta G, RARECARE working group contributing to the data quality study

Abstract
PURPOSE: Rare cancers represent 22% of all tumors in Europe; however, the quality of the data of rare cancers may not be as good as the quality of data for common cancer. The project surveillance of rare cancers in Europe (RARECARE) had, among others, the objective of assessing rare cancer data quality in population-based cancer registries (CRs). Eight rare cancers were considered: mesothelioma, liver angiosarcoma, sarcomas, tumors of oral cavity, CNS tumors, germ cell tumors, leukemia, and malignant digestive endocrine tumors.
METHODS: We selected data on 18,000 diagnoses and revised, on the basis of the pathologic and clinical reports (but not on pathologic specimens), unspecified morphology and topography codes originally attributed by CR officers and checked the quality of follow-up of long-term survivors of poor prognosis cancers.
RESULTS: A total of 38 CRs contributed from 13 European countries. The majority of unspecified morphology and topography cases were confirmed as unspecified. The few unspecified cases that, after the review, changed to a more specific diagnosis increased the incidence of the common cancer histotypes. For example, 11% of the oral cavity epithelial cancers were reclassified from unspecified to more specific diagnoses: 8% were reclassified as squamous cell carcinoma (commoner) and only 1% as adenocarcinoma (rarer). The revision confirmed the majority of long-term survivors revealing a relative high proportion of mesothelioma long-term survivors. The majority of appendix carcinoids changed behavior from malignant to borderline lesions.
CONCLUSIONS: Our study suggests that the problem of poorly specified morphology and topography cases is mainly one of difficulty in reaching a precise diagnosis. The awareness of the importance of data quality for rare cancers should increase among registrars, pathologists, and clinicians.

PMID: 27716878 [PubMed - indexed for MEDLINE]

Abnormal increase of intraocular pressure in fellow eye after severe ocular trauma: A case report.

Medicine (Baltimore). 2016 Aug;95(31):e4411

Authors: Vaajanen A, Tuulonen A

Abstract
BACKGROUND: An ocular injury can lead to secondary glaucoma in the traumatized eye in 3% to 20% of cases. Literature on the risk of developing elevated intraocular pressure in the nontraumatized fellow eye is scant. Clinicians treating ocular traumas should also bear in mind sympathetic ophthalmia, a rare bilateral granulomatous panuveitis following accidental or surgical trauma to 1 eye.
CASE REPORT: We report a case of high-pressure glaucoma of the fellow eye without any signs of uveitis. The left eye of a 24-year-old man was injured in an inadvertent movement during a free-time table-tennis match. The eye was severely crushed, leading to blindness. His right eye developed medically uncontrolled high-pressure glaucoma only 1 month after the injury.
CONCLUSION: To the best of our knowledge, there are no previous reports of post-traumatic glaucoma in the nontraumatized eye after open-globe injury.

PMID: 27495058 [PubMed - indexed for MEDLINE]