title: Extrathoracic investigation in adult patients with isolated pulmonary langerhans cell histiocytosis.
abstract: BACKGROUND
  An important objective on diagnosis of patients with Langerhans cell histiocytosis (LCH) is to determine the extent of disease. However, whether systematic extrathoracic investigation is needed in adult patients with clinically isolated pulmonary LCH (PLCH) has not been evaluated.
  
  
  METHODS
  In this prospective, multicentre study, 54 consecutive patients with newly diagnosed clinically isolated PLCH were systematically evaluated at inclusion by bone imaging and blood laboratory testing to search for subclinical extrapulmonary LCH involvement. The patients were followed over a 2-year period. At each visit, they were asked about the presence of extrapulmonary manifestations of LCH.
  
  
  RESULTS
  In the absence of bone symptoms, the skeletal X-ray survey results were normal for all but two patients who had a localised bone lesion consistent with possible LCH involvement, that remained unchanged over 2 years of follow-up. Whole-body bone scintigraphy did not add information to the plain radiography findings for the detection of asymptomatic bone involvement in isolated PLCH. Conversely, it showed nonspecific focal bone uptake in 18% of the patients, mainly corresponding to post-traumatic or degenerative abnormalities unrelated to LCH. Mild leucocytosis due to neutrophilia was observed in 22% of the patients and was not related to their smoking habits. Three patients had mild isolated lymphocytosis without haematological disease, whereas two patients had mild lymphopaenia. A mild inflammatory biological syndrome was observed in a minority of patients without infection or constitutional symptoms and was not associated with progressive disease. A substantial proportion (24.5%) of the patients had abnormal biological liver test results, including elevated liver enzymes and/or cholestasis, which were not linked to LCH involvement in this cohort.
  
  
  CONCLUSIONS
  Obtaining a thorough history and performing comprehensive physical examination are essential for staging patients diagnosed with PLCH. In the absence of symptoms or signs suggestive of extrapulmonary LCH involvement, the systematic performing of recommended bone imaging does not appear informative. Although the observed blood laboratory abnormalities were not specifically related to LCH, performing these tests in the diagnostic workup for PLCH is useful because some of these alterations may impact patient management.
  
  
  BACKGROUND
  ClinicalTrials.gov: No. NCT01225601; URL: www.clinicaltrials.gov.
authors.affiliation: Assistance Publique-Hôpitaux de Paris, Hôpital Saint-Louis, Centre National de Référence de l'histiocytose Langerhansienne, Service de Pneumologie, 1 Avenue Claude Vellefaux, 75475 cedex 10, Paris, France. abdellatif.tazi@sls.aphp.fr.|Université Paris Diderot, Sorbonne Paris Cité, U1153 CRESS, Biostatistics and Clinical Epidemiology research team, Paris, France. abdellatif.tazi@sls.aphp.fr.
authors.forename: Abdellatif
authors.initials: A
authors.lastname: Tazi
authors.affiliation: Assistance Publique-Hôpitaux de Paris, Service de Radiologie, Hôpital Saint-Louis, Paris, France.
authors.forename: Constance
authors.initials: C
authors.lastname: de Margerie-Mellon
authors.affiliation: Assistance Publique-Hôpitaux de Paris, Service de Médecine Nucléaire, Hôpital Saint-Louis, Paris, France.
authors.forename: Laetitia
authors.initials: L
authors.lastname: Vercellino
authors.affiliation: Assistance Publique-Hôpitaux de Paris, Service de Pneumologie, Hôpital Avicenne, Bobigny, France.
authors.forename: Jean Marc
authors.initials: JM
authors.lastname: Naccache
authors.affiliation: Service de Pneumologie et Immuno-allergologie, Centre de compétence des maladies pulmonaires rares, Hôpital Calmette, Lille, France.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Fry
authors.affiliation: Département de Pneumologie, Hôpital Charles Nicolle, Rouen, France.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Dominique
authors.affiliation: IRSET UMR 1085, Université de Rennes 1; Service de Pneumologie, Hôpital Pontchaillou, Rennes, France.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Jouneau
authors.affiliation: Assistance Publique-Hôpitaux de Paris, Hôpital Saint-Louis, Centre National de Référence de l'histiocytose Langerhansienne, Service de Pneumologie, 1 Avenue Claude Vellefaux, 75475 cedex 10, Paris, France.
authors.forename: Gwenaël
authors.initials: G
authors.lastname: Lorillon
authors.affiliation: Assistance Publique-Hôpitaux de Paris, Hôpital Saint-Louis, Centre National de Référence de l'histiocytose Langerhansienne, Service de Pneumologie, 1 Avenue Claude Vellefaux, 75475 cedex 10, Paris, France.
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Bugnet
authors.affiliation: Département de Pneumologie, Hôpital Arnaud de Villeneuve, Montpellier, France.
authors.forename: Raphael
authors.initials: R
authors.lastname: Chiron
authors.affiliation: Service de Pneumologie et Immuno-allergologie, Centre de compétence des maladies pulmonaires rares, Hôpital Calmette, Lille, France.|Université Lille 2, Lille, France.
authors.forename: Benoit
authors.initials: B
authors.lastname: Wallaert
authors.affiliation: Université Paris 13, Sorbonne Paris Cité; Assistance Publique-Hôpitaux de Paris, Service de Pneumologie, Hôpital Avicenne, Bobigny, France.
authors.forename: Dominique
authors.initials: D
authors.lastname: Valeyre
authors.affiliation: Université Paris Diderot, Sorbonne Paris Cité, U1153 CRESS, Biostatistics and Clinical Epidemiology research team, Paris, France.|Assistance Publique-Hôpitaux de Paris; Hôpital Saint-Louis, Service de Biostatistique et Information Médicale, Paris, France.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Chevret
mesh_terms: D000328:Adult; D001842:Bone and Bones / Q000000981:diagnostic imaging; D005260:Female; D006646:Histiocytosis, Langerhans-Cell / Q000175:diagnosis*; D006801:Humans; D008168:Lung / Q000473:pathology; D008297:Male; D011446:Prospective Studies; D011859:Radiography
references.citation: Intern Med. 2001 Oct;40(10):998-1003
references.pmid: 11688843
references.citation: Am J Respir Crit Care Med. 1996 Jan;153(1):426-35
references.pmid: 8542154
references.citation: Hematol Oncol Clin North Am. 1998 Apr;12(2):369-78
references.pmid: 9561906
references.citation: J Nucl Med. 1996 Sep;37(9):1456-60
references.pmid: 8790192
references.citation: Pediatr Radiol. 1987;17(5):397-404
references.pmid: 2819814
references.citation: Intern Med. 2007;46(15):1231-5
references.pmid: 17675775
references.citation: Chest. 2007 May;131(5):1557-66
references.pmid: 17494805
references.citation: Cancer. 1999 May 15;85(10):2278-90
references.pmid: 10326709
references.citation: Orphanet J Rare Dis. 2012;7:16
references.pmid: 22429393
references.citation: Medicine (Baltimore). 1981 Nov;60(6):385-96
references.pmid: 6975871
references.citation: Eur Respir J. 2006 Jun;27(6):1272-85
references.pmid: 16772390
references.citation: Am J Respir Crit Care Med. 2012 Nov 1;186(9):930-2
references.pmid: 23118088
references.citation: Am J Surg Pathol. 1993 Oct;17(10):971-86
references.pmid: 8372949
references.citation: Med Pediatr Oncol. 1997 Jan;28(1):9-14
references.pmid: 8950330
references.citation: Eur J Cancer. 2003 Nov;39(16):2341-8
references.pmid: 14556926
references.citation: Clin Res Hepatol Gastroenterol. 2011 Jun;35(6-7):475-81
references.pmid: 21550330
references.citation: Orphanet J Rare Dis. 2014;9:191
references.pmid: 25433492
references.citation: Recent Pat Anticancer Drug Discov. 2006 Jan;1(1):23-38
references.pmid: 18221024
references.citation: Respiration. 1993;60(1):38-44
references.pmid: 8469818
references.citation: Eur J Intern Med. 2015 Jun;26(5):351-6
references.pmid: 25899682
references.citation: N Engl J Med. 2002 Feb 14;346(7):484-90
references.pmid: 11844849
references.citation: Case Rep Radiol. 2015;2015:536328
references.pmid: 25977828
references.citation: Pediatr Blood Cancer. 2009 Jan;52(1):97-101
references.pmid: 18951435
references.citation: Eur J Haematol. 2006 May;76(5):363-8
references.pmid: 16548916
references.citation: Eur Respir Rev. 2010 Mar;19(115):86-8
references.pmid: 20956172
references.citation: Orphanet J Rare Dis. 2013;8:72
references.pmid: 23672541
references.citation: Orphanet J Rare Dis. 2015;10:30
references.pmid: 25887097
references.citation: Radiographics. 1995 Sep;15(5):1135-46
references.pmid: 7501855
references.citation: Sarcoidosis Vasc Diffuse Lung Dis. 2012 Oct;29(2):132-8
references.pmid: 23461076