{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T18:56:14Z","timestamp":1780080974957,"version":"3.54.0"},"reference-count":35,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,3,5]],"date-time":"2021-03-05T00:00:00Z","timestamp":1614902400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2021,3,5]],"date-time":"2021-03-05T00:00:00Z","timestamp":1614902400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Orphanet J Rare Dis"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Mastocytosis is a rare disease characterised by the accumulation and\/or proliferation of abnormal mast cells (MCs) in one or several organs. It may present with a number of different symptoms that involve various organ systems. The current study aims to assess the prevalence of MC mediator-related symptoms in a cohort of mastocytosis patients with a specific focus on neurological, psychiatric, cognitive and sexual symptoms. We also assessed the impact of the disease on patients\u2019 professional lives. Patients were administered a validated multidimensional questionnaire to collect information on patients\u2019 perception of the severity of their symptoms. From the questionnaires we extracted the neurological, cognitive, psychiatric and sexual symptoms and the impact of the disease on patients\u2019 professional lives as well as their grading. The affective status was assessed using the 17-item version of the Hamilton Depression Rating Scale.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We included 139 patients. Mastocytosis was classified as systemic in 113 patients and cutaneous in 26 patients. The prevalence of MC mediator-related systemic symptoms was as follows: cutaneous (71%), gastro-intestinal (48%), cardio-vascular (36%), musculoskeletal (26.6%), fatigue (24%), urinary (14.4%) and respiratory (10%). Headaches and vertigo were noted in respectively 55% and 32% of patients. Irritability, episodes of memory loss and difficulty concentrating were reported in 54%, 52% and 40% of cases, respectively. Sexual impairment was noted in 24% of patients. No associations were found between neuropsychiatric\/cognitive impairment and age, gender, diagnostic delay, disease form, the presence of cutaneous lesions, the level of serum and bone marrow tryptase and the presence of KIT mutation in bone marrow and\/or skin. Depression was noted in 49% of patients. One in four patients reported a negative impact of the disease on their professional lives.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This current study provides some insights regarding symptoms related to mastocytosis and their impact on patients\u2019 professional lives.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s13023-021-01747-y","type":"journal-article","created":{"date-parts":[[2021,3,5]],"date-time":"2021-03-05T05:04:31Z","timestamp":1614920671000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Neuropsychiatric, cognitive and sexual impairment in mastocytosis patients"],"prefix":"10.1186","volume":"16","author":[{"given":"Fatma","family":"Jendoubi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maella","family":"Severino-Freire","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mathilde","family":"Negretto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christophe","family":"Arbus","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carle","family":"Paul","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5275-6868","authenticated-orcid":false,"given":"Cristina","family":"Bulai Livideanu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,3,5]]},"reference":[{"issue":"3","key":"1747_CR1","doi-asserted-by":"publisher","first-page":"215","DOI":"10.1159\/000328760","volume":"157","author":"P Valent","year":"2012","unstructured":"Valent P, Akin C, Arock M, Brockow K, Butterfield JH, Carter MC, et al. Definitions, criteria and global classification of mast cell disorders with special reference to mast cell activation syndromes: a consensus proposal. Int Arch Allergy Immunol. 2012;157(3):215\u201325.","journal-title":"Int Arch Allergy Immunol"},{"issue":"4","key":"1747_CR2","doi-asserted-by":"publisher","first-page":"521","DOI":"10.1111\/bjh.12916","volume":"166","author":"S Cohen","year":"2014","unstructured":"Cohen S, Skovbo S, Vestergaard H, Kristensen T, M\u00f8ller M, Bindslev-Jensen C, Fryzek J, Broesby-Olsen S. Epidemiology of systemic mastocytosis in Denmark. Br J Haematol. 2014;166(4):521\u20138.","journal-title":"Br J Haematol"},{"issue":"9","key":"1747_CR3","doi-asserted-by":"publisher","first-page":"1713","DOI":"10.1111\/jdv.15638","volume":"33","author":"M Fradet","year":"2019","unstructured":"Fradet M, Negretto M, Tournier E, Laurent C, Apoil PA, Evrard S, et al. Frequency of isolated cutaneous involvement in adult mastocytosis: a cohort study. J Eur Acad Dermatol Venereol. 2019;33(9):1713\u20138.","journal-title":"J Eur Acad Dermatol Venereol"},{"issue":"11","key":"1747_CR4","doi-asserted-by":"publisher","first-page":"1420","DOI":"10.1182\/blood-2016-09-731893","volume":"129","author":"P Valent","year":"2017","unstructured":"Valent P, Akin C, Metcalfe DD. Mastocytosis: 2016 updated WHO classification and novel emerging treatment concepts. Blood. 2017;129(11):1420\u20137.","journal-title":"Blood"},{"issue":"6","key":"1747_CR5","doi-asserted-by":"publisher","first-page":"869","DOI":"10.1111\/all.12842","volume":"71","author":"F Siebenhaar","year":"2016","unstructured":"Siebenhaar F, von Tschirnhaus E, Hartmann K, Rabenhorst A, Staubach P, Peveling-Oberhag A, et al. Development and validation of the mastocytosis quality of life questionnaire: MC-QoL. Allergy. 2016;71(6):869\u201377.","journal-title":"Allergy"},{"issue":"5","key":"1747_CR6","doi-asserted-by":"publisher","first-page":"e2266","DOI":"10.1371\/journal.pone.0002266","volume":"3","author":"O Hermine","year":"2008","unstructured":"Hermine O, Lortholary O, Leventhal PS, Catteau A, Soppelsa F, Baude C, et al. Case-control cohort study of patients\u2019 perceptions of disability in mastocytosis. PLoS ONE. 2008;3(5):e2266.","journal-title":"PLoS ONE"},{"key":"1747_CR7","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1136\/jnnp.23.1.56","volume":"23","author":"M Hamilton","year":"1960","unstructured":"Hamilton M. A rating scale for depression. J Neurol Neurosurg Psychiatry. 1960;23:56\u201362.","journal-title":"J Neurol Neurosurg Psychiatry"},{"issue":"2","key":"1747_CR8","doi-asserted-by":"publisher","first-page":"384","DOI":"10.1016\/j.jad.2013.04.028","volume":"150","author":"M Zimmerman","year":"2013","unstructured":"Zimmerman M, Martinez JH, Young D, Chelminski I, Dalrymple K. Severity classification on the Hamilton Depression Rating Scale. J Affect Disord. 2013;150(2):384\u20138.","journal-title":"J Affect Disord"},{"issue":"3","key":"1747_CR9","doi-asserted-by":"publisher","first-page":"451","DOI":"10.1016\/j.iac.2006.05.010","volume":"26","author":"LB Schwartz","year":"2006","unstructured":"Schwartz LB. Diagnostic value of tryptase in anaphylaxis and mastocytosis. Immunol Allergy Clin North Am. 2006;26(3):451\u201363.","journal-title":"Immunol Allergy Clin North Am"},{"issue":"3","key":"1747_CR10","doi-asserted-by":"publisher","first-page":"453","DOI":"10.1016\/j.jaad.2006.09.020","volume":"56","author":"J Proelss","year":"2007","unstructured":"Proelss J, Wenzel J, Ko Y, Bieber T, Bauer R. Tryptase detection in bone-marrow blood: a new diagnostic tool in systemic mastocytosis. J Am Acad Dermatol. 2007;56(3):453\u20137.","journal-title":"J Am Acad Dermatol"},{"issue":"1","key":"1747_CR11","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1111\/cea.12627","volume":"46","author":"C Bulai Livideanu","year":"2016","unstructured":"Bulai Livideanu C, Apoil PA, Lepage B, Eischen M, Laurent C, Laharrague P, et al. Bone marrow tryptase as a possible diagnostic criterion for adult systemic mastocytosis. Clin Exp Allergy. 2016;46(1):133\u201341.","journal-title":"Clin Exp Allergy"},{"issue":"15","key":"1747_CR12","doi-asserted-by":"publisher","first-page":"1522","DOI":"10.1177\/0333102411421683","volume":"31","author":"JH Smith","year":"2011","unstructured":"Smith JH, Butterfield JH, Cutrer FM. Primary headache syndromes in systemic mastocytosis. Cephalalgia. 2011;31(15):1522\u201331.","journal-title":"Cephalalgia"},{"issue":"7","key":"1747_CR13","doi-asserted-by":"publisher","first-page":"570","DOI":"10.1016\/j.clineuro.2011.05.002","volume":"113","author":"JH Smith","year":"2011","unstructured":"Smith JH, Butterfield JH, Pardanani A, DeLuca GC, Cutrer FM. Neurologic symptoms and diagnosis in adults with mast cell disease. Clin Neurol Neurosurg. 2011;113(7):570\u20134.","journal-title":"Clin Neurol Neurosurg"},{"issue":"9","key":"1747_CR14","doi-asserted-by":"publisher","first-page":"465","DOI":"10.1056\/NEJM197908303010903","volume":"301","author":"NA Soter","year":"1979","unstructured":"Soter NA, Austen KF, Wasserman SI. Oral disodium cromoglycate in the treatment of systemic mastocytosis. N Engl J Med. 1979;301(9):465\u20139.","journal-title":"N Engl J Med"},{"issue":"6","key":"1747_CR15","doi-asserted-by":"publisher","first-page":"437","DOI":"10.1097\/00006842-198607000-00006","volume":"48","author":"MP Rogers","year":"1986","unstructured":"Rogers MP, Bloomingdale K, Murawski BJ, Soter NA, Reich P, Austen KF. Mixed organic brain syndrome as a manifestation of systemic mastocytosis. Psychosom Med. 1986;48(6):437\u201347.","journal-title":"Psychosom Med"},{"issue":"6","key":"1747_CR16","doi-asserted-by":"publisher","first-page":"e39468","DOI":"10.1371\/journal.pone.0039468","volume":"7","author":"DS Moura","year":"2012","unstructured":"Moura DS, Sultan S, Georgin-Lavialle S, Barete S, Lortholary O, Gaillard R, et al. Evidence for cognitive impairment in mastocytosis: prevalence, features and correlations to depression. PLoS ONE. 2012;7(6):e39468.","journal-title":"PLoS ONE"},{"issue":"1\u20132","key":"1747_CR17","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.jad.2007.06.006","volume":"106","author":"AE Castaneda","year":"2008","unstructured":"Castaneda AE, Tuulio-Henriksson A, Marttunen M, Suvisaari J, Lonnqvist J. A review on cognitive impairments in depressive and anxiety disorders with a focus on young adults. J Affect Disord. 2008;106(1\u20132):1\u201327.","journal-title":"J Affect Disord"},{"issue":"10","key":"1747_CR18","doi-asserted-by":"publisher","first-page":"e26375","DOI":"10.1371\/journal.pone.0026375","volume":"6","author":"DS Moura","year":"2011","unstructured":"Moura DS, Sultan S, Georgin-Lavialle S, Pillet N, Montestruc F, Gineste P, et al. Depression in patients with mastocytosis: prevalence, features and effects of masitinib therapy. PLoS ONE. 2011;6(10):e26375.","journal-title":"PLoS ONE"},{"issue":"12","key":"1747_CR19","doi-asserted-by":"publisher","first-page":"921","DOI":"10.1002\/ajh.21894","volume":"85","author":"C Paul","year":"2010","unstructured":"Paul C, Sans B, Suarez F, Casassus P, Barete S, Lanternier F, et al. Masitinib for the treatment of systemic and cutaneous mastocytosis with handicap: a phase 2a study. Am J Hematol. 2010;85(12):921\u20135.","journal-title":"Am J Hematol"},{"issue":"9","key":"1747_CR20","doi-asserted-by":"publisher","first-page":"732","DOI":"10.1016\/j.biopsych.2008.11.029","volume":"65","author":"AH Miller","year":"2009","unstructured":"Miller AH, Maletic V, Raison CL. Inflammation and its discontents: the role of cytokines in the pathophysiology of major depression. Biol Psychiatry. 2009;65(9):732\u201341.","journal-title":"Biol Psychiatry"},{"key":"1747_CR21","doi-asserted-by":"publisher","first-page":"104","DOI":"10.1186\/1477-7525-8-104","volume":"8","author":"EA Laugsand","year":"2010","unstructured":"Laugsand EA, Sprangers MA, Bjordal K, Skorpen F, Kaasa S, Klepstad P. Health care providers underestimate symptom intensities of cancer patients: a multicenter European study. Health Qual Life Outcomes. 2010;8:104.","journal-title":"Health Qual Life Outcomes"},{"issue":"7","key":"1747_CR22","doi-asserted-by":"publisher","first-page":"477","DOI":"10.1007\/s005200100244","volume":"9","author":"F Stiefel","year":"2001","unstructured":"Stiefel F, Die Trill M, Berney A, Olarte JM, Razavi A. Depression in palliative care: a pragmatic report from the Expert Working Group of the European Association for Palliative Care. Support Care Cancer. 2001;9(7):477\u201388.","journal-title":"Support Care Cancer"},{"issue":"4","key":"1747_CR23","doi-asserted-by":"publisher","first-page":"383","DOI":"10.1176\/appi.psy.50.4.383","volume":"50","author":"KM Brintzenhofe-Szoc","year":"2009","unstructured":"Brintzenhofe-Szoc KM, Levin TT, Li Y, Kissane DW, Zabora JR. Mixed anxiety\/depression symptoms in a large cancer cohort: prevalence by cancer type. Psychosomatics. 2009;50(4):383\u201391.","journal-title":"Psychosomatics"},{"issue":"2 Pt 3","key":"1747_CR24","first-page":"S21","volume":"29","author":"S Sultan","year":"2003","unstructured":"Sultan S, Hartemann-Heurtier A, Grimaldi A. Understanding patients to promote self-regulation in Type 2 diabetes: how to live with an illness beginning before its onset? Diabetes Metab. 2003;29(2 Pt 3):S21-30.","journal-title":"Diabetes Metab"},{"issue":"8","key":"1747_CR25","doi-asserted-by":"publisher","first-page":"e1197","DOI":"10.1038\/tp.2017.137","volume":"7","author":"N Boddaert","year":"2017","unstructured":"Boddaert N, Salvador A, Chandesris MO, Lema\u00eetre H, Gr\u00e9vent D, Gauthier C, Naggara O, Georgin-Lavialle S, Moura DS, Munsch F, Jaafari N, Zilbovicius M, Lortholary O, Gaillard R, Hermine O. Neuroimaging evidence of brain abnormalities in mastocytosis. Transl Psychiatry. 2017;7(8):e1197.","journal-title":"Transl Psychiatry"},{"issue":"1\u20132","key":"1747_CR26","doi-asserted-by":"publisher","first-page":"166","DOI":"10.1016\/j.pain.2007.03.012","volume":"130","author":"D Levy","year":"2007","unstructured":"Levy D, Burstein R, Kainz V, Jakubowski M, Strassman AM. Mast cell degranulation activates a pain pathway underlying migraine headache. Pain. 2007;130(1\u20132):166\u201376.","journal-title":"Pain"},{"issue":"2","key":"1747_CR27","doi-asserted-by":"publisher","first-page":"423","DOI":"10.1097\/00001756-199902050-00039","volume":"10","author":"M Hasselblatt","year":"1999","unstructured":"Hasselblatt M, Kohler J, Volles E, Ehrenreich H. Simultaneous monitoring of endothelin-1 and vasopressin plasma levels in migraine. NeuroReport. 1999;10(2):423\u20135.","journal-title":"NeuroReport"},{"issue":"2","key":"1747_CR28","doi-asserted-by":"publisher","first-page":"158","DOI":"10.1046\/j.1526-4610.2000.00022.x","volume":"40","author":"F Sheftell","year":"2000","unstructured":"Sheftell F, Rapoport A, Weeks R, Walker B, Gammerman I, Baskin S. Montelukast in the prophylaxis of migraine: a potential role for leukotriene modifiers. Headache. 2000;40(2):158\u201363.","journal-title":"Headache"},{"issue":"2","key":"1747_CR29","doi-asserted-by":"publisher","first-page":"200","DOI":"10.1111\/j.1526-4610.2006.00337.x","volume":"46","author":"P Sarchielli","year":"2006","unstructured":"Sarchielli P, Alberti A, Baldi A, Coppola F, Rossi C, Pierguidi L, et al. Proinflammatory cytokines, adhesion molecules, and lymphocyte integrin expression in the internal jugular blood of migraine patients without aura assessed ictally. Headache. 2006;46(2):200\u20137.","journal-title":"Headache"},{"issue":"11","key":"1747_CR30","doi-asserted-by":"publisher","first-page":"1511","DOI":"10.1038\/mp.2015.216","volume":"21","author":"S Georgin-Lavialle","year":"2016","unstructured":"Georgin-Lavialle S, Moura DS, Salvador A, Chauvet-Gelinier JC, Launay JM, Damaj G, et al. Mast cells\u2019 involvement in inflammation pathways linked to depression: evidence in mastocytosis. Mol Psychiatry. 2016;21(11):1511\u20136.","journal-title":"Mol Psychiatry"},{"key":"1747_CR31","doi-asserted-by":"publisher","first-page":"703","DOI":"10.3389\/fnins.2017.00703","volume":"11","author":"D Kempuraj","year":"2017","unstructured":"Kempuraj D, Selvakumar GP, Thangavel R, Ahmed ME, Zaheer S, Raikwar SP, et al. Mast cell activation in brain injury, stress, and post-traumatic stress disorder and Alzheimer\u2019s disease pathogenesis. Front Neurosci. 2017;11:703.","journal-title":"Front Neurosci"},{"issue":"3\u20134","key":"1747_CR32","first-page":"845","volume":"17","author":"WM Purcell","year":"1996","unstructured":"Purcell WM, Westgate C, Atterwill CK. Rat brain mast cells: an in vitro paradigm for assessing the toxic effects of neurotropic therapeutics. Neurotoxicology. 1996;17(3\u20134):845\u201350.","journal-title":"Neurotoxicology"},{"issue":"3","key":"1747_CR33","doi-asserted-by":"publisher","first-page":"1487","DOI":"10.1007\/s12035-014-8697-6","volume":"49","author":"H Dong","year":"2014","unstructured":"Dong H, Zhang W, Zeng X, Hu G, Zhang H, He S, et al. Histamine induces upregulated expression of histamine receptors and increases release of inflammatory mediators from microglia. Mol Neurobiol. 2014;49(3):1487\u2013500.","journal-title":"Mol Neurobiol"},{"issue":"12","key":"1747_CR34","doi-asserted-by":"publisher","first-page":"618","DOI":"10.1016\/S0166-2236(00)01661-1","volume":"23","author":"NJ Rothwell","year":"2000","unstructured":"Rothwell NJ, Luheshi GN. Interleukin 1 in the brain: biology, pathology and therapeutic target. Trends Neurosci. 2000;23(12):618\u201325.","journal-title":"Trends Neurosci"},{"issue":"1","key":"1747_CR35","doi-asserted-by":"publisher","first-page":"70","DOI":"10.1016\/j.jaip.2013.09.004","volume":"2","author":"S Jennings","year":"2014","unstructured":"Jennings S, Russell N, Jennings B, Slee V, Sterling L, Castells M, et al. The Mastocytosis Society survey on mast cell disorders: patient experiences and perceptions. J Allergy Clin Immunol Pract. 2014;2(1):70\u20136.","journal-title":"J Allergy Clin Immunol Pract"}],"container-title":["Orphanet Journal of Rare Diseases"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s13023-021-01747-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1186\/s13023-021-01747-y\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s13023-021-01747-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,3,5]],"date-time":"2021-03-05T05:05:33Z","timestamp":1614920733000},"score":1,"resource":{"primary":{"URL":"https:\/\/ojrd.biomedcentral.com\/articles\/10.1186\/s13023-021-01747-y"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,3,5]]},"references-count":35,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2021,12]]}},"alternative-id":["1747"],"URL":"https:\/\/doi.org\/10.1186\/s13023-021-01747-y","relation":{"has-preprint":[{"id-type":"doi","id":"10.21203\/rs.3.rs-96772\/v2","asserted-by":"object"},{"id-type":"doi","id":"10.21203\/rs.3.rs-96772\/v1","asserted-by":"object"}]},"ISSN":["1750-1172"],"issn-type":[{"value":"1750-1172","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,3,5]]},"assertion":[{"value":"19 October 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 February 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"5 March 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The study was approved by the Institutional Review Board of the Necker Enfants-Malades Hospital on November 8, 2000 (RC31\/17\/0095) and was carried out in accordance with the Declaration of Helsinki.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"All patients gave their written informed consent.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"Fatma Jendoubi, Mathilde Negretto, Maella Severino-Freire, Christophe Arbus, Cristina Bulai Livideanu and Carle Paul declare they have no conflict of interest regarding this epidemiological study.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"118"}}