Aktuelle Neurologie 2017; 44(10): 733-741
DOI: 10.1055/s-0043-115530
Originalarbeit
© Georg Thieme Verlag KG Stuttgart · New York

Choosing wisely? Multiple Sklerose und laborchemische Suche nach autoimmunen Differenzialdiagnosen – Sind die Leitlinien-Empfehlungen der Deutschen Gesellschaft für Neurologie dazu sinnvoll?

Laboratory Screening for Autoimmune Differential Diagnoses in Multiple Sclerosis: Do the Guideline Recommendations of the German Society of Neurology Make Sense?
Jana Becker*
Alfried Krupp Hospital Essen, Department of Neurology and Neurophysiology, Essen
,
Mareike Geffken*
Alfried Krupp Hospital Essen, Department of Neurology and Neurophysiology, Essen
,
Rolf R. Diehl
Alfried Krupp Hospital Essen, Department of Neurology and Neurophysiology, Essen
,
Peter Berlit
Alfried Krupp Hospital Essen, Department of Neurology and Neurophysiology, Essen
,
Markus Krämer
Alfried Krupp Hospital Essen, Department of Neurology and Neurophysiology, Essen
› Author Affiliations
Further Information

Publication History

Publication Date:
17 October 2017 (online)

Zusammenfassung

Einführung Eine Vielzahl von Erkrankungen können das Bild einer Multiplen Sklerose (MS) imitieren. Bei der Erstdiagnose der MS wird der Ausschluss von Differenzialdiagnosen gefordert. Die Leitlinien der Deutschen Gesellschaft für Neurologie empfehlen die Analyse von 13 obligaten und 9 fakultativen Laborparametern. Zu den obligaten Empfehlungen gehören die Bestimmung der antinukleären Antikörper (ANA) und der Antikörper gegen Doppelstrang-DNS (ds-DNA-AK).

Methodik In der Kohorte einer MS-Ambulanz wurden diejenigen Datensätze ausgewertet, bei denen zumindest teilweise die empfohlenen Laborparameter analysiert wurden. Daneben wurden MRT-Daten, Familienanamnese, klinische Präsentation, evozierte Potenziale und Liquorbefunde erfasst. Prospektiv wurde ein Fragebogen zu differenzialdiagnostisch relevanten rheumatologischen Symptomen eingesetzt.

Ergebnisse Von 554 Patienten, die sich mit Verdacht auf MS in einer MS-Ambulanz vorstellten, waren bei 197 Patienten zumindest teilweise die differenzialdiagnostisch geforderten Laborparameter analysiert worden. Bei 124 Patienten konnte eine MS bestätigt werden. Bei 117 Patienten (59 %) des Gesamtkollektivs mit 197 Patienten waren die ANA mit mindestens einem Titer von 1:80 auffällig. Von den 124 MS-Patienten hatten 68 (55 %) einen positiven ANA-Titer von mindestens 1:80. Weder ANA noch ANCA oder ds-DNA-AK konnten zwischen MS und Nicht-MS unterscheiden. MS-Patienten mit einem positiven ANA-Titer von 1:80 litten häufiger an Autoimmunerkrankungen und hatten eine positive Familienanamnese für MS. Von den 73 Patienten ohne MS waren 49 (67 %) ANA-positiv. In dieser Patientengruppe waren die ANA-positiven Patienten häufiger psychiatrisch erkrankt. Bei den befragten Patienten mit einem ANA-Titer > 1:160 war innerhalb von durchschnittlich 1,9 Jahren keine rheumatologische Erkrankung diagnostiziert worden.

Zusammenfassung In Anlehnung an die amerikanischen „choosing wisely“-Empfehlungen für rheumatologische Erkrankungen erscheint ein obligates breites Laborscreening bei der Erstdiagnose der Multiplen Sklerose ohne konkrete differenzialdiagnostische Verdachtsdiagnose nicht sinnvoll.

Abstract

Introduction A variety of diseases can mimic the presentation of multiple sclerosis (MS). Diagnosing MS requires the exclusion of differential diagnoses. The guidelines of the German Society of Neurology (DGN) recommend analyzing 13 obligatory and nine facultative laboratory parameters. The obligatory recommendations include antinuclear antibodies (ANA) as well as the antibodies against double-stranded DNA (ds-DNA-Ab).

Methods In a cohort of MS outpatients, records were analyzed, in which the laboratory parameters were taken into consideration at least partially. In addition to the laboratory parameters, MRI data, family history, clinical presentation, evoked potentials, and CSF findings were analyzed.

Results: Of 554 patients, the differential diagnostic laboratory parameters were available in 197 patients at least partially. In 59.4 % of these 197 patients, the ANA were elevated to at least a titer of 1:80. Neither ANA nor ANCA nor ds-DNA-Ab was able to distinguish between MS and non-MS; 54.8 % of 124 MS patients had a positive ANA titer of at least 1:80. MS patients with this titer suffered more frequently from autoimmune diseases and had a family history of MS. Of the remaining 73 patients without MS, 67.1 % were ANA positive. In this patient population, the ANA-positive patients were more frequently diagnosed with psychiatric diseases.

Conclusion According to the American “choosing wisely” recommendations for rheumatologic diseases, obligatory laboratory screening appears to be inappropriate in the initial diagnosis of multiple sclerosis without a specific differential diagnostic reason.

* gleichberechtigte Erstautoren


 
  • Literatur

  • 1 Polman CH, Reingold SC, Banwell B. et al. Diagnostic criteria for multiple sclerosis: 2010 revisions to the McDonald criteria. Ann Neurol 2011; 69: 292-302
  • 2 Swanton JK, Rovira A, Tintore M. et al. MRI criteria for multiple sclerosis in patients presenting with clinically isolated syndromes: a multicentre retrospective study. Lancet Neurol 2007; 6: 677-686
  • 3 Kollia K, Maderwald S, Putzki N. et al. First clinical study on ultra-high-field MR imaging in patients with multiple sclerosis: comparison of 1.5T and 7T. AJNR Am J Neuroradiol 2009; 30: 699-702
  • 4 Dixon JE, Simpson A, Mistry N. et al. Optimisation of T(2)*-weighted MRI for the detection of small veins in multiple sclerosis at 3 T and 7 T. Eur J Radiol 2013; 82: 719-727
  • 5 Gold R, Hemmer B, Wiendl H. Leitlinie Diagnose und Therapie der Multiplen Sklerose. In: Diener HC, Weimar C. Hrsg. Leitlinien für Diagnostik und Therapie in der Neurologie. Stuttgart: Thieme Verlag; 2014
  • 6 Arinuma Y, Kikuchi H, Wada T. et al. Brain MRI in patients with diffuse psychiatric/neuropsychological syndromes in systemic lupus erythematosus. Lupus Sci Med 2014; 1: e000050
  • 7 Saruhan-Direskeneli G, Yentur SP, Mutlu M. et al. Intrathecal oligoclonal IgG bands are infrequently found in neuro-Behcetʼs disease. Clin Exp Rheumatol 2013; 31: 25-27
  • 8 Chabriat H, Joutel A, Dichgans M. et al. Cadasil. Lancet Neurol 2009; 8: 643-653
  • 9 Bottcher T, Rolfs A, Tanislav C. et al. Fabry disease – underestimated in the differential diagnosis of multiple sclerosis?. PLoS One 2013; 8: e71894
  • 10 Becker J, Rolfs A, Karabul N. et al. D313Y mutation in the differential diagnosis of white matter lesions: experiences from a multiple sclerosis outpatient clinic. Mult Scler 2016; 22: 1502-1505
  • 11 Karussis D, Leker RR, Ashkenazi A. et al. A subgroup of multiple sclerosis patients with anticardiolipin antibodies and unusual clinical manifestations: do they represent a new nosological entity?. Ann Neurol 1998; 44: 629-634
  • 12 Heinzlef O, Weill B, Johanet C. et al. Anticardiolipin antibodies in patients with multiple sclerosis do not represent a subgroup of patients according to clinical, familial, and biological characteristics. J Neurol Neurosurg Psychiatry 2002; 72: 647-649
  • 13 Barned S, Goodman AD, Mattson DH. Frequency of anti-nuclear antibodies in multiple sclerosis. Neurology 1995; 45: 384-385
  • 14 Collard RC, Koehler RP, Mattson DH. Frequency and significance of antinuclear antibodies in multiple sclerosis. Neurology 1997; 49: 857-861
  • 15 Garg N, Zivadinov R, Ramanathan M. et al. Clinical and MRI correlates of autoreactive antibodies in multiple sclerosis patients. J Neuroimmunol 2007; 187: 159-165
  • 16 Etemadifar M, Fatemi A, Hashemijazi H. et al. Is it necessary to perform connective tissue disorders laboratory tests when a patient experiences the first demyelinating attack?. J Res Med Sci 2013; 18: 617-620
  • 17 Solomon AJ, Klein EP, Bourdette D. “Undiagnosing” multiple sclerosis: the challenge of misdiagnosis in MS. Neurology 2012; 78: 1986-1991
  • 18 Chow SL, Carter Thorne J, Bell MJ. et al. Choosing wisely: the Canadian Rheumatology Associationʼs list of 5 items physicians and patients should question. J Rheumatol 2015; 42: 682-689
  • 19 Ferrari R. Evaluation of the Canadian Rheumatology Association Choosing Wisely recommendation concerning anti-nuclear antibody (ANA) testing. Clin Rheumatol 2015; 34: 1551-1556
  • 20 Rouster-Stevens KA, Ardoin SP, Cooper AM. et al. Choosing Wisely: the American College of Rheumatologyʼs Top 5 for pediatric rheumatology. Arthritis Care Res 2014; 66: 649-657
  • 21 Kavanaugh A, Tomar R, Reveille J. et al. Guidelines for clinical use of the antinuclear antibody test and tests for specific autoantibodies to nuclear antigens. American College of Pathologists. Arch Pathol Lab Med 2000; 124: 71-81
  • 22 Fritzler MJ. Choosing wisely: Review and commentary on anti-nuclear antibody (ANA) testing. Autoimmun Rev 2016; 15: 272-280
  • 23 Verstegen G, Duyck MC, Meeus P. et al. Detection and identification of antinuclear antibodies (ANA) in a large community hospital. Acta Clin Belg 2009; 64: 317-323
  • 24 Tintore M, Rovira A, Rio J. et al. Do oligoclonal bands add information to MRI in first attacks of multiple sclerosis?. Neurology 2008; 70: 1079-1083
  • 25 Tan EM, Feltkamp TE, Smolen JS. et al. Range of antinuclear antibodies in “healthy” individuals. Arthritis Rheum 1997; 40: 1601-1611
  • 26 Vaile JH, Dyke L, Kherani R. et al. Is high titre ANA specific for connective tissue disease?. Clin Exp Rheumatol 2000; 18: 433-438
  • 27 Illei GG, Klippel JH. Why is the ANA result positive?. Bull Rheum Dis 1999; 48: 1-4
  • 28 Barcellos LF, Kamdar BB, Ramsay PP. et al. Clustering of autoimmune diseases in families with a high-risk for multiple sclerosis: a descriptive study. Lancet Neurol 2006; 5: 924-931
  • 29 Broadley SA, Deans J, Sawcer SJ. et al. Autoimmune disease in first-degree relatives of patients with multiple sclerosis. A UK survey. Brain 2000; 123: 1102-1111
  • 30 Ramagopalan SV, Dyment DA, Valdar W. et al. Autoimmune disease in families with multiple sclerosis: a population-based study. Lancet Neurol 2007; 6: 604-610
  • 31 Farez MF, Balbuena Aguirre ME, Varela F. et al. Autoimmune disease prevalence in a multiple sclerosis cohort in Argentina. Mult Scler Int 2014; 2014: 828162