A Rare Case of Q Fever Osteomyelitis in a Child From Regional Australia.

J Pediatric Infect Dis Soc. 2015 Sep;4(3):e28-31

Authors: Britton PN, Macartney K, Arbuckle S, Little D, Kesson A

Abstract
Q fever osteomyelitis is a rare disease. We report an eighth pediatric case from regional Australia. Serology is the first-line diagnostic test, with confirmation by PCR on tissue specimens. In endemic settings, Q fever should be considered in the differential diagnosis of chronic osteomyelitis; in particular, presumed chronic-recurrent multifocal osteomyelitis should be considered a possible presentation of Q fever osteo-articular disease in children.

PMID: 26407439 [PubMed - indexed for MEDLINE]

Fertility in adult women with classic galactosemia and primary ovarian insufficiency.

Fertil Steril. 2017 Jul;108(1):168-174

Authors: van Erven B, Berry GT, Cassiman D, Connolly G, Forga M, Gautschi M, Gubbels CS, Hollak CEM, Janssen MC, Knerr I, Labrune P, Langendonk JG, Õunap K, Thijs A, Vos R, Wortmann SB, Rubio-Gozalbo ME

Abstract
OBJECTIVE: To study pregnancy chance in adult women with classic galactosemia and primary ovarian insufficiency. Despite dietary treatment, >90% of women with classic galactosemia develop primary ovarian insufficiency, resulting in impaired fertility. For many years, chance of spontaneous conception has not been considered, leading to counseling for infertility. But an increasing number of reports on pregnancies in this group questions whether current counseling approaches are correct.
DESIGN: Multicenter retrospective observational study.
SETTING: Metabolic centers.
PATIENT(S): Adult women (aged >18 y) with confirmed classic galactosemia and primary ovarian insufficiency were included.
INTERVENTION(S): Participants and medical records were consulted to obtain study data in a standardized manner with the use of a questionnaire.
MAIN OUTCOME MEASURE(S): Conception opportunities, time to pregnancy, pregnancy outcome, hormone replacement therapy use, fertility counseling, and the participants' vision of fertility were evaluated. Potential predictive factors for increased pregnancy chance were explored.
RESULT(S): Eighty-five women with classic galactosemia and primary ovarian insufficiency participated. Twenty-one women actively attempted to conceive or did not take adequate contraceptive precautions. Of these 21 women, nine became pregnant spontaneously (42.9%). This was higher than reported in primary ovarian insufficiency due to other causes (5%-10%). After a period of 12 months, a cumulative proportion of 27.8% of couples had conceived, which increased to 48.4% after 24 months and 61.3% after 27 months. Predictive factors could not be identified. A considerable miscarriage rate of 30% was observed (6 of 20 pregnancies). Although a substantial proportion of women expressed a child-wish (n = 28/53; 52.8%), the vast majority of participants (n = 43/57; 75.4%) considered conceiving to be highly unlikely, owing to negative counseling in the past.
CONCLUSION(S): The pregnancy rate in women with classic galactosemia and primary ovarian insufficiency was higher than for women with primary ovarian insufficiency of any cause. This shifting paradigm carries significant implications for fertility counseling and potential application of fertility preservation techniques.

PMID: 28579413 [PubMed - indexed for MEDLINE]

Epidermolysis bullosa House Austria and Epidermolysis bullosa clinical network : Example of a centre of expertise implemented in a European reference network to face the burden of a rare disease.

Wien Klin Wochenschr. 2017 Jan;129(1-2):1-7

Authors: Laimer M, Pohla-Gubo G, Diem A, Prodinger C, Bauer JW, Hintner H

Abstract
Accurately addressing the diverse and complex issues of rare diseases (RD) in terms of prevention, recognition, diagnosis, treatment, care and research along key RD specificities, such as great heterogeneity, a limited number of patients, scarcity of relevant knowledge and expertise as well as enormous costs for patient care is a challenging task for healthcare providers and authorities that makes a supranational approach particularly feasible. The European Union has acknowledged RD matters by several initiatives, including efforts to implement national centres of expertise and European reference networks as well as a cross-border referral mechanism to foster access to expert services and to boost dissemination of clinical expertise and research activities. Exemplified by the EB House Austria, a centre of expertise for epidermolysis bullosa cross-linked with international reference partner institutions, this strategy proves its potential to be translated into optimized patient care and to meet the major medical, scientific, social and health-economic impact of RD.

PMID: 27909793 [PubMed - indexed for MEDLINE]

["Manubriosternal Synchondrosis": A Rare Problem in Sports Medicine].

Sportverletz Sportschaden. 2016 Dec;30(4):229-231

Authors: Rist A, Willscheid G, Rasch H, Paul J

Abstract
Non-traumatic, inflammatory and painful lesions of the manubriosternal joint are rare pathologies and, to our knowledge, have not been described in the literature of sports medicine. We report the case of a 30-year-old male strength athlete who developed chronic pain in the manubriosternal joint after exercise. Four-month abstinence from exercise combined with a conservative rehabilitation program performed after clinical and radiological tests did not bring any symptomatic relief. After a local ultrasound-guided single-shot sclerotherapy procedure performed in our clinic, the patient was free of symptoms and quickly regained his ability to exercise.

PMID: 27825179 [PubMed - indexed for MEDLINE]

[Rare Conjunctival Metastasis in Cancer of Unknown Primary Syndrome].

Klin Monbl Augenheilkd. 2016 May;233(5):644-6

Authors: Paul S, Vogelgesang S, Tost FH

PMID: 27187886 [PubMed - indexed for MEDLINE]

Adult prostatic sarcoma: A contemporary multicenter Rare Cancer Network study.

Prostate. 2017 Jul;77(10):1160-1166

Authors: De Bari B, Stish B, Ball MW, Habboush Y, Sargos P, Krengli M, Bossi A, Stabile A, Sole Pesutic C, Lestrade L, Smeenk RJ, Jereczek-Fossa BA, Zilli T, Créhange G, Alongi F, Zaorsky N, Ozsahin M

Abstract
INTRODUCTION: Adult prostatic sarcoma (PS) is a rare disease. While surgery is considered the standard approach, the role of other therapies is not completely established. We report results of the largest multicentric contemporary cohort of PS patients.
MATERIALS AND METHODS: This study included 61 adult PS patients treated in 16 American and European Institutions. Median age was 64.4 years (range: 22-87). Curative surgery was delivered in 48 patients (prostatectomy = 26, cystoprostatectomy = 22), usually with lymphadenectomy (n = 40). Curative radiotherapy (RT) was delivered in 32 patients, as radical (n = 5), neoadjuvant (n = 10), or postoperative treatment (n = 17). Eighteen patients received chemotherapy. None of the patients received hormonal therapy.
RESULTS: Median follow-up was 72 months (95%CI: 55-not reached). Five-year local control (LC), overall survival (OS), cancer-specific survival, disease-free survival, and metastases-free rates were 47%, 53%, 56%, 35%, and 35%, respectively. Notably, curative RT (neoadjuvant, adjuvant, or definitive) was associated with improved 5-year LC (55% vs. 31%, P = 0.02) and OS (59% vs. 46%, P = 0.1). Surgically treated patients presenting with a cT3-4 tumor (n = 31), who received RT (n = 24), had a significantly improved 5-year LC (68% vs, 33%, P = 0.004) and OS (65% vs. 21%, P < 0.001) rates compared to patients not receiving RT. cT4 patients demonstrated a significantly lower 5-year OS (43% vs. 61%, P = 0.006) and LC (29% vs. 69%, P < 0.001) rates. Histologic subtype was not associated with LC and OS, but patients with prostatic stromal sarcoma, rhabdomyosarcoma, or sarcomatoid carcinoma had worse 5-year LC compared to other types (47% vs. 55%) and OS (49% vs. 58%).
CONCLUSION: Adult PS has a poor prognosis. Locally advanced tumors have poor LC and OS rates. Curative RT should be considered part of the multidisciplinary approach to PS.

PMID: 28594087 [PubMed - indexed for MEDLINE]

[Endometritis : Rare disease with clinical importance?]

Pathologe. 2016 Nov;37(6):521-525

Authors: Lax SF

Abstract
Endometritis is nowadays rare in developed countries and typically shows a subclinical or mild course; therefore, there are probably more cases of endometritis than diagnosed but they lack clinical relevance. In the fertile period of life it can be the reason for vaginal bleeding and infertility. The most common causes for non-specific endometritis are residual placental tissue after abortion or childbirth, intrauterine interventions, lesions within the uterine cavity, such as endometrial polyps, endometrial hyperplasia and neoplasms, intrauterine devices (IUD) and cervical stenosis. The histological detection of plasma cells in the endometrial stroma is required for the diagnosis of chronic endometritis. These can be detected immunohistochemically using anti-CD138 antibodies, which should be carried out particularly in cases of infertility with only slight inflammatory symptoms and few plasma cells. The use of an IUD containing progestin is frequently associated with an asymptomatic lymphoplasmacytic infiltration. After curettage or endometrial biopsy, an eosinophilic xanthogranulomatous or granulomatous endometritis and also a foreign body granuloma reaction can occur. Specific forms of endometritis, such as caused by tuberculosis, sarcoidosis, mycoplasma and herpes are very rare. Cytomegalovirus endometritis is associated with immunosuppression. Endometritis caused by infections with Chlamydia trachomatis is characterized by an extensive lymphoplasmacytic infiltration. The differential diagnoses of chronic endometritis include the very rare malignant lymphoma, which is usually characterized by a relatively monotonous cell infiltration.

PMID: 27738813 [PubMed - indexed for MEDLINE]

[Q fever : A rare differential diagnosis of granulomatous disease].

Pathologe. 2016 May;37(3):269-74

Authors: Hippe S, Kellner N, Seliger G, Wiechmann V, Grünewald T

Abstract
Q fever is a worldwide distributed zoonotic disease with a mostly benign course, which regularly reoccurs in Germany. This report is about a patient with sporadic serologically proven Q fever, which also showed typical histopathological findings with nonspecific granulomatous hepatitis, usually seen in acute disease. The bone marrow biopsy revealed so-called doughnut granulomas, which are not pathognomonic but a typical finding in Q fever. This case report impressively underlines that the histomorphological findings can make a decisive contribution to the clarification by extended differential diagnostics, even though it plays a subordinate role in the routine diagnostics of disseminated Q fever.

PMID: 26919849 [PubMed - indexed for MEDLINE]

Clinical Practice Guidelines for Rare Diseases: The Orphanet Database.

PLoS One. 2017;12(1):e0170365

Authors: Pavan S, Rommel K, Mateo Marquina ME, Höhn S, Lanneau V, Rath A

Abstract
Clinical practice guidelines (CPGs) for rare diseases (RDs) are scarce, may be difficult to identify through Internet searches and may vary in quality depending on the source and methodology used. In order to contribute to the improvement of the diagnosis, treatment and care of patients, Orphanet (www.orpha.net) has set up a procedure for the selection, quality evaluation and dissemination of CPGs, with the aim to provide easy access to relevant, accurate and specific recommendations for the management of RDs. This article provides an analysis of selected CPGs by medical domain coverage, prevalence of diseases, languages and type of producer, and addresses the variability in CPG quality and availability. CPGs are identified via bibliographic databases, websites of research networks, expert centres or medical societies. They are assessed according to quality criteria derived from the Appraisal of Guidelines, REsearch and Evaluation (AGREE II) Instrument. Only open access CPGs and documents for which permission from the copyright holders has been obtained are disseminated on the Orphanet website. From January 2012 to July 2015, 277 CPGs were disseminated, representing coverage of 1,122 groups of diseases, diseases or subtypes in the Orphanet database. No language restriction is applied, and so far 10 languages are represented, with a predominance of CPGs in English, French and German (92% of all CPGs). A large proportion of diseases with identified CPGs belong to rare oncologic, neurologic, hematologic diseases or developmental anomalies. The Orphanet project on CPG collection, evaluation and dissemination is a continuous process, with regular addition of new guidelines, and updates. CPGs meeting the quality criteria are integrated to the Orphanet database of rare diseases, together with other types of textual information and the appropriate services for patients, researchers and healthcare professionals in 40 countries.

PMID: 28099516 [PubMed - indexed for MEDLINE]

Improving treatment results with reference centres for rare cancers: where do we stand?

Eur J Cancer. 2017 May;77:90-98

Authors: Ray-Coquard I, Pujade Lauraine E, Le Cesne A, Pautier P, Vacher Lavenue MC, Trama A, Casali P, Coindre JM, Blay JY

Abstract
Rare adult cancer (RAC) is characterised by an incidence of less than six cases per 100,000 people per annum; 4,300,000 patients in the European Union are living with rare cancer (22% of all new human cancers). These cancers are linked with worse survival rates than 'frequent' tumours (5-year survival: 47% for RAC against 65% for 'common' cancers), mainly because of: (1) delays in obtaining an accurate diagnosis, (2) inadequate treatments given in curative phases and (3) restricted opportunities for patients to participate in clinical trials because of the lack of support for dedicated trials for this disease group from both academic and industrial sponsors. Although quantitative studies to measure the socioeconomic burden of RACs as a whole are still lacking, the increasing fragmentation of all cancers into molecular subgroups implies a substantial increase in the number of RACs and their associated socioeconomic burden. To answer this urgent and growing need, some countries, cooperative groups, and cancer institutes delineated national and/or regional organisations to promote quality management for RACs. Currently, the European Union (EU) is supporting an official EU call to organise a European network dedicated to RACs. The goals will be to pool the vast knowledge and expertise of the 67 EU clinical reference centres and to cover ten rare adult solid cancer domains across more than 18 countries in order to deploy an integrated, EU-wide capacity towards accelerated innovative treatments and care for RACs while empowering patients. This article will summarise these experiences and the potential benefit for patients.

PMID: 28384534 [PubMed - indexed for MEDLINE]

An unusual case of chondrolysis of the hip: a possible etiology for a rare condition - a case report.

J Pediatr Orthop B. 2016 Nov;25(6):533-8

Authors: Ruiz Picazo D, Doñate Pérez F, Jiménez Ortega P, Gaspar Aparicio N

Abstract
UNLABELLED: Idiopathic chondrolysis of the hip (ICH) is a rare condition of unknown etiology, and is characterized by rapid, progressive destruction of the articular cartilage in the coxofemoral joint. This condition has an insidious onset, and is observed more commonly in female preadolescents. Patients report intense pain, motion restriction, and often present with an antalgic gait. Medical imaging techniques are required to make a differential diagnosis and biological markers for inflammation and infection should be evaluated. Avascular necrosis, septic arthritis, and juvenile idiopathic arthritis are the primary alternatives that should be precluded before making a diagnosis. Conservative treatment focuses on pain control and preservation of joint mobility. However, surgical treatment may be an option for these patients. We present a rare case of a 10-year-old boy where imaging tests and physical examination were consistent with conventional idiopathic hip chondrolysis. Following hip joint biopsy and culture, we observed the presence of bacteria originating from the mouth, which could have been responsible for the pathogenesis of ICH. This is the first report of ICH in which common bacteria of the mouth were found upon joint biopsy. In addition, with respect to the pathogenesis of hip chondrolysis, this case emphasizes that numerous factors are involved, many of which remain unknown.
LEVEL OF EVIDENCE: V.

PMID: 27243805 [PubMed - indexed for MEDLINE]

Rare Diseases on the Internet: An Assessment of the Quality of Online Information.

J Med Internet Res. 2017 Jan 18;19(1):e23

Authors: Pauer F, Litzkendorf S, Göbel J, Storf H, Zeidler J, Graf von der Schulenburg JM

Abstract
BACKGROUND: The importance of the Internet as a medium for publishing and sharing health and medical information has increased considerably during the last decade. Nonetheless, comprehensive knowledge and information are scarce and difficult to find, especially for rare diseases. Additionally, the quality of health or medical information about rare diseases is frequently difficult to assess for the patients and their family members.
OBJECTIVE: The aim of this study is to assess the quality of information on the Internet about rare diseases. Additionally, the study aims to evaluate if the quality of information on rare diseases varies between different information supplier categories.
METHODS: A total of 13 quality criteria for websites providing medical information about rare diseases were transferred to a self-disclosure questionnaire. Identified providers of information on the Internet about rare diseases were invited to fill out the questionnaire. The questionnaire contained questions about the information provider in general (eg, supplier category, information category, language, use of quality certificates, and target group) and about quality aspects that reflect the 13 quality criteria. Differences in subgroup analyses were performed using t tests.
RESULTS: We identified 693 websites containing information about rare diseases. A total of 123 questionnaires (17.7%) were completely filled out by the information suppliers. For the remaining identified suppliers (570/693, 82.3%), the questionnaires were filled out by the authors based on the information available on their website. In many cases, the quality of websites was proportionally low. Furthermore, subgroup analysis showed no statistically significant differences between the quality of information provided by support group/patient organization compared to medical institution (P=.19). The quality of information by individuals (patient/relative) was significantly lower compared to information provided by support group/patient organization (P=.001), medical institution (P=.009), and other associations and sponsoring bodies (P=.001) as well.
CONCLUSIONS: Overall, the quality of information on the Internet about rare diseases is low. Quality certificates are rarely used and important quality criteria are often not fulfilled completely. Additionally, some information categories are underrepresented (eg, information about psychosocial counseling, social-legal advice, and family planning). Nevertheless, due to the high amount of information provided by support groups, this study shows that these are extremely valuable sources of information for patients suffering from a rare disease and their relatives.

PMID: 28100442 [PubMed - indexed for MEDLINE]

12 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 2017/08/10

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.

Intoxication and substance use disorder to Areca catechu nut containing betel quid: A review of epidemiological evidence, pharmacological basis and social factors influencing quitting strategies.

Drug Alcohol Depend. 2017 Jul 29;179:187-197

Authors: Osborne PG, Ko YC, Wu MT, Lee CH

Abstract
AIM: We present a systematic review of substance use disorder (SUD) to Areca catechu nut (AN) and AN containing betel quid (ANcBQ) with emphasis on dependence resulting from chewing of tobacco-free ANcBQ. We examined pharmacology of intoxication and addiction, and factors influencing quitting strategies.
METHODS: Epidemiological publications of SUD were included according to PRISMA criteria. Pharmacological publications were retrieved from the PUBMED database and websites of the WHO, United Nations, and Sigma-Aldrich.
RESULTS: Nine epidemiological studies show clear evidence of abuse and dependence in tobacco-free ANcBQ and/or ANcBQ+Tobacco chewers. Dependency is greater if ANcBQ contains tobacco. In both groups higher dependency scores were positively correlated with higher frequency of chewing. Dependency on AN+Lime is associated with altered brain morphology, resting state brain activity, neurochemistry and deterioration of working spatial memory. ANcBQ contains a complex mixture of neuroactive compounds that have the potential to act directly upon all major cerebral neurotransmitter systems. Of these compounds, only arecoline (muscarinic agonist) has been the focus of limited pharmacological investigation. In animal studies, arecoline increases dopamine transmission in the mesocorticolimbic circuit and this action may be one factor contributing to ANcBQ dependency in humans. Societal and familial acceptance of ANcBQ consumption is paramount for commencement and persistence of chewing.
CONCLUSIONS: ANcBQ SUD remains an orphan disease. The limited understanding of pharmacological basis of intoxication and SUD determines there are no pharmacological replacement therapies for ANcBQ SUD. The addictive properties of ANcBQ coupled with social acceptance of ANcBQ chewing limits the effectiveness of counseling-based quitting programs.

PMID: 28787696 [PubMed - as supplied by publisher]

Inherited platelet disorders: toward DNA-based diagnosis.

Blood. 2016 Jun 09;127(23):2814-23

Authors: Lentaigne C, Freson K, Laffan MA, Turro E, Ouwehand WH, BRIDGE-BPD Consortium and the ThromboGenomics Consortium

Abstract
Variations in platelet number, volume, and function are largely genetically controlled, and many loci associated with platelet traits have been identified by genome-wide association studies (GWASs).(1) The genome also contains a large number of rare variants, of which a tiny fraction underlies the inherited diseases of humans. Research over the last 3 decades has led to the discovery of 51 genes harboring variants responsible for inherited platelet disorders (IPDs). However, the majority of patients with an IPD still do not receive a molecular diagnosis. Alongside the scientific interest, molecular or genetic diagnosis is important for patients. There is increasing recognition that a number of IPDs are associated with severe pathologies, including an increased risk of malignancy, and a definitive diagnosis can inform prognosis and care. In this review, we give an overview of these disorders grouped according to their effect on platelet biology and their clinical characteristics. We also discuss the challenge of identifying candidate genes and causal variants therein, how IPDs have been historically diagnosed, and how this is changing with the introduction of high-throughput sequencing. Finally, we describe how integration of large genomic, epigenomic, and phenotypic datasets, including whole genome sequencing data, GWASs, epigenomic profiling, protein-protein interaction networks, and standardized clinical phenotype coding, will drive the discovery of novel mechanisms of disease in the near future to improve patient diagnosis and management.

PMID: 27095789 [PubMed - indexed for MEDLINE]

15 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 2017/08/08

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.

Depression and Hypersomnia: A Complex Association.

Sleep Med Clin. 2017 Sep;12(3):395-405

Authors: Lopez R, Barateau L, Evangelista E, Dauvilliers Y

Abstract
Hypersomnolence is a clinically defined syndrome characterized by the association of prolonged nocturnal sleep, impaired arousal quality, and sleep inertia. Hypersomnolence is the major feature of central hypersomnias and is frequently reported in various mood disorders, such as major depressive disorder, bipolar disorder, or seasonal affective disorder. Assessment of hypersomnolence is challenging in depressed patients, with objective tests often in the normal range despite a high level of sleepiness complaint. On the other hand, many patients with central hypersomnias reported depressive symptoms. The self-assessment of mood symptoms in patients with central hypersomnias may overdiagnose depression with an overlap between both conditions.

PMID: 28778237 [PubMed - in process]

Heterozygous De Novo UBTF Gain-of-Function Variant Is Associated with Neurodegeneration in Childhood.

Am J Hum Genet. 2017 Aug 03;101(2):267-273

Authors: Edvardson S, Nicolae CM, Agrawal PB, Mignot C, Payne K, Prasad AN, Prasad C, Sadler L, Nava C, Mullen TE, Begtrup A, Baskin B, Powis Z, Shaag A, Keren B, Moldovan GL, Elpeleg O

Abstract
Ribosomal RNA (rRNA) is transcribed from rDNA by RNA polymerase I (Pol I) to produce the 45S precursor of the 28S, 5.8S, and 18S rRNA components of the ribosome. Two transcription factors have been defined for Pol I in mammals, the selectivity factor SL1, and the upstream binding transcription factor (UBF), which interacts with the upstream control element to facilitate the assembly of the transcription initiation complex including SL1 and Pol I. In seven unrelated affected individuals, all suffering from developmental regression starting at 2.5-7 years, we identified a heterozygous variant, c.628G>A in UBTF, encoding p.Glu210Lys in UBF, which occurred de novo in all cases. While the levels of UBF, Ser388 phosphorylated UBF, and other Pol I-related components (POLR1E, TAF1A, and TAF1C) remained unchanged in cells of an affected individual, the variant conferred gain of function to UBF, manifesting by markedly increased UBF binding to the rDNA promoter and to the 5'- external transcribed spacer. This was associated with significantly increased 18S expression, and enlarged nucleoli which were reduced in number per cell. The data link neurodegeneration in childhood with altered rDNA chromatin status and rRNA metabolism.

PMID: 28777933 [PubMed - in process]

High oxygen affinity hemoglobins.

Rev Med Interne. 2017 Feb;38(2):106-112

Authors: Mangin O

Abstract
High oxygen affinity hemoglobins are responsible for rare and heterogeneous autosomic dominant genetic diseases. They cause pure erythrocytosis, sometimes accountable for hyperviscosity and thrombosis, or hemolysis. Differential diagnoses must be first ruled out. The diagnosis is based on the identification of a decreased P50, and their possible characterization by cation exchange-high performance liquid chromatography and capillary electrophoresis. Finally, genetic studies of the responsible globin chain gene will confirm the mutation. The prognosis mainly relies on the P50 decrease rate and on the hemoglobin cooperativity impairment. Disease management should be personalized, and it should primarily depend on smoking cessation and physical activity. Phlebotomy and platelet aggregation inhibitors' prescriptions can be discussed. There is no contraindication to flights, high-altitude conditions, or pregnancy. Nevertheless, blood donation must be prohibited.

PMID: 27637720 [PubMed - indexed for MEDLINE]

Role of B cells in the pathogenesis of systemic sclerosis.

Rev Med Interne. 2017 Feb;38(2):113-124

Authors: Sanges S, Guerrier T, Launay D, Lefèvre G, Labalette M, Forestier A, Sobanski V, Corli J, Hauspie C, Jendoubi M, Yakoub-Agha I, Hatron PY, Hachulla E, Dubucquoi S

Abstract
Systemic sclerosis (SSc) is an orphan disease characterized by progressive fibrosis of the skin and internal organs. Aside from vasculopathy and fibrotic processes, its pathogenesis involves an aberrant activation of immune cells, among which B cells seem to play a significant role. Indeed, B cell homeostasis is disturbed during SSc: the memory subset is activated and displays an increased susceptibility to apoptosis, which is responsible for their decreased number. This chronic loss of B cells enhances bone marrow production of the naïve subset that accounts for their increased number in peripheral blood. This permanent activation state can be explained mainly by two mechanisms: a dysregulation of B cell receptor (BCR) signaling, and an overproduction of B cell survival signals, B cell activating factor (BAFF) and a proliferation-inducing ligand (APRIL). These disturbances of B cell homeostasis induce several functional anomalies that participate in the inflammatory and fibrotic events observed during SSc: autoantibody production (some being directly pathogenic); secretion of pro-inflammatory and pro-fibrotic cytokines (interleukin-6); direct cooperation with other SSc-involved cells [fibroblasts, through transforming growth factor-β (TGF-β) signaling, and T cells]. These data justify the evaluation of anti-B cell strategies as therapeutic options for SSc, such as B cell depletion or blockage of B cell survival signaling.

PMID: 27020403 [PubMed - indexed for MEDLINE]