The significance of cerebrospinal fluid examination in neuropsychiatric systemic lupus erythematosus
Authors:
V. Balajková; M. Olejárová
Authors place of work:
Revmatologická klinika 1. LF UK, Praha
; Revmatologický ústav, Praha
Published in the journal:
Čes. Revmatol., 26, 2018, No. 1, p. 23-33.
Category:
Review Article
Summary
Neuropsychiatric systemic lupus erythematosus (NPSLE) is a serious complication of this disease which significantly degrades the quality of life of the patient. This is one of the most complex manifestations of systemic lupus, which can affect the central, peripheral and autonomic nervous system. The exact pathophysiology of this disease is not known yet, neither is a specific biomarker for its detection. The neurological examination of cerebrospinal fluid has received more attention in recent years, especially in the NPSLE diagnostic algorithm. Besides standard cytological, biochemical and immunological examinations, it also offers the possibility of detection of autoantibodies, inflammatory mediators and blood-brain barrier disorders.
The aim of this work is to summarize the most frequent findings in patients with neuropsychiatric involvement in systemic lupus erythematosus. The most common type of cellular response in NPSLE is mild pleocytosis with a majority of lymphocytes, and neutrophilic granulocytosis in transverse myelitis. In the biochemical examination of the cerebrospinal fluid, in up to half of the cases the total protein and the albumin quotient were increased, indicating damage to the blood-brain barrier. A frequent finding is also an increase in the IgG index and detection of intrathecal oligoclonal IgG synthesis. Of the pro-inflammatory cytokines, IL-6 and IL-8 are present in most cases of NPSLE. Proteins that are associated with NPSLE include anti-RP, anti-N, anti-U1RNP and anti-Sm antibodies.
Key words:
neuropsychiatric systemic lupus erythematosus, cerebrospinal fluid
Zdroje
1. Bertsias GK, Boumpas DT. Pathogenesis, diagnosis and management of neuropsychiatric SLE manifestations. Nat Rev Rheumatol 2010; 6(6): 358–67.
2. Yazdany J. Health-related quality of life measurement in adult systemic lupus erythematosus: Lupus Quality of Life (LupusQoL), Systemic Lupus Erythematosus-Specific Quality of Life Questionnaire (SLEQOL), and Systemic Lupus Erythematosus Quality of Life Questionnaire (L-QoL). Arthritis Care Res (Hoboken) 2011; 63 (Suppl 11): S413–9.
3. Bortoluzzi A, Scirè CA, Bombardieri S, Caniatti L, Conti F, De Vita S, et al. Development and validation of a new algorithm for attribution of neuropsychiatric events in systemic lupus erythematosus. Rheumatology (Oxford) 2015; 54(5): 891–8.
4. Brey RL, Holliday SL, Saklad AR, Navarrete MG, Hermosillo-Romo D, Stallworth CL, et al. Neuropsychiatric syndromes in lupus: prevalence using standardized definitions. Neurology 2002; 58(8): 1214–20.
5. Joseph FG, Scolding NJ. Neurolupus. Pract Neurol 2010; 10(1): 4–15.
6. Sibbitt WL, Jr., Brandt JR, Johnson CR, Maldonado ME, Patel SR, Ford CC, et al. The incidence and prevalence of neuropsychiatric syndromes in pediatric onset systemic lupus erythematosus. J Rheumatol 2002; 29(7): 1536–42.
7. The American College of Rheumatology nomenclature and case definitions for neuropsychiatric lupus syndromes. Arthritis Rheum 1999; 42(4): 599–608.
8. Govoni M, Bortoluzzi A, Padovan M et al. The diagnosis and clinical management of the neuropsychiatric manifestation of lupus. Journal Autoimmuny 2016; 74: 41–72.
9. Rožnovský L. Neuroinfekce v intenzivní péči. Neurol prax 2013; 14(5): 258–2.
10. Adam P, Táborský L, Průcha M, Sobek O, Kratochvíla J, Zeman D. Cerebrospinal fluid cytology. A Monograph. Prague, Medica News Publishers, 2000.
11. Feinglass EJ, Arnett FC, Dorsch CA, et al. Neuropsychiatric manifestation of systemic lupus erythematosus: diagnosis, clinical spectrum and relationship to others features of the disease. Medicine 1976; 55(4); 323–339.
12. Boumpas DT, Patronas NJ, Dalakas MC, et al. Acute transverse myelitis in systemic lupus erythematosus: magnetic resonance imaging and review of the literature. J Rheumatol 1990; 17(1): 89–92.
13. Abialmouna J, Shoemaker DW, Pullicino PM and Baer AN. Marked cerebrospinal fluid pleocytosis in systemic lupus erythematosus related cerebral ischemia. J Rheumatol 1992; 19(4): 626–9.
14. Gibson T, Myers AR. Nervous system involvement in systemic lupus erythematosus. Ann Rheum Dis 1975; 35(5): 398–406.
15. Pierce R, Logothetis J. Spinal fluid pleocytosis in systemic lupus erythematosus. J Lancet 1962; 82: 458–60.
16. Canosa JJ, Cohen AS. Aseptic meningitis in systemic lupus erythematosus: report of three cases. Arthritis Rheum 1975; 18: 369 – 73.
17. Goswani D, Shuddosatta Ch, Ahmad BI, Shabtanu D. Two cases reports indicating the dilemma in diagnosis lupus cerebritis. J Family Med Prim Care 2013; 2(1): 111–114.
18. Zhao YH, Shao YG, Ren HT et al. Cerebrospinal fluid cytology studies of neuropsychiatric systemic lupus erythematosus. Chin J Contemp Neurol Neurosurg 2013; 13(2): 132–5.
19. Adam P, Peterová V, Dostál C, Seidl Z, Obenberger J, Olejárová M, et al. Likvorologické nálezy u systémového lupus erythematodes s postižením CNS. Klin Biochem Metab 1998; 6 (27): 35–9.
20. Neuwelt CM, Young RG. Managing neuropsychiatric lupus: Top 10 clinical pearls. J Muscoskelet Med 2009; 26: 127–35.
21. Abbott NJ, Mendonca LL, Dolman DE. The blood-brain barrier in systemic lupus erythematosus. Lupus 2003; 12: 908–15.
22. Sakuma Y, Nagai T, Yoshio T, Hirohata S. Differential activation mechanism of serum C5a in lupus iritis and neuropsychiatric systemic lupus erythematosus. Mod Rheumatol 2017; 27(2): 292–297.
23. Hirohata S, Sakuma Y, Yanagida T, Yoshioy T. Association of cerebrospinal fluid anti-Sm antibodies with acute confusional state in systemic lupus erythematosus. Arthritis Res Ther 2014; 16(5): 450.
24. Stojanovich L, Smiljanich-Milijkovich D, Omdal R and Sakic B. Neuropsychiatric lupus and association with cerebrospinal fluid immunoglobulins: A pilot study. Isr Med ASIC J 2009; 11(6): 359–62.
25. Alexander JJ, Quigg RJ. Systemic lupus erythematosus and the brain: what mice are telling us. Neurochem Int 2007; 50: 5–11.
26. Sidor MM, Sakic B, Malinowski PM, Ballock DA, Oleschuk CJ, Macri J. Elevated immunoglobulin levels in the cerebrospinal fluid from lupus-prone mice. J Neuroimmunol 2005; 165: 104–13.
27. Zameer A, Hoffman SA. Immunoglobulin binding to brain in autoimmune mice. J Neuroimmunol 2001; 120: 10–8.
28. Sobek O, Adam P, Keilbich P et al. Vyšetření likvoru – současné možnosti. Neurol praxi 2009; 10(5): 280–4.
29. Deisenhamer F, Bartoš A, Egg R, Gilhus NE, Giovannoni G, Rauer S, et al. Guidelines on routine cerebrospinal fluid analysis. Report from EFNS task force. Eur J Neurol 2006; 13: 913–22.
30. Freedman MS, Thompson EJ, Deisenhamer F, Giovannoni G, Grimsley G, Keir G et al. Recommended standard of cerebrospinal fluid analysis in the diagnosis of multiple sclerosis. A consensus statement. Archive Neurol 2005; 62: 865–70.
31. Miller JR. Burke AM, Bever CT. Occurrence of oligoclonal bands in multiple sclerosis and other CNS disease. Ann Neurol 1983; 13: 53–8.
32. Link H Kostulas V. Utility of isoelectric focusing of cerebrospinal fluid and serum on agarose evaluated for neurological patients. Clin Chem 1983; 29: 810–5.
33. Wielfield JB, Shaw M, Silverman LM et al. Intrathecal Ig synthesis and blood-brain barrier impairment in patients with systemic lupus erythematosus and central nervous system dysfunction. Am J Med 1983; 74: 837–44.
34. McLean BN, Miller D, Thompson EJ. Oligoclonal banding of IgG in CSF, blood-brain barrier function, and MRI findings in patients with sarcoidosis, systemic lupus erythematosus, and Bechcet´s disease involving the nervous system. J Neurol Neurosurg Psychiatry 1995; 58: 548–54.
35. West SG, Emlen W, Wener MH, Kotin BL. Neuropsychiatric lupus erythematosus: a 10-year prospective study on the value of diagnostic test. Am J Med 1995; 99(2): 153–63.
36. Gulati G, Iffland PH, Janigro D, Zhag B,Luggen ME. Anti-NR2 antibodies, blood-brain barrier and cognitive dysfunction. Clin Rheumatol 2016; 35(12): 2989–97.
37. Fragoso-Loyo H, Cabiedes J, Atisha-Fregoso Y, Llorente L, Sanchéz-Guerrero J. Utility of serum S100B protein for identification of central nervous system involvement in systemic lupus erythematosus. J Rheumatol 2010; 37 (11): 2280 –5.
38. Brunner HI, Klein-Gitelman MS, Zelko F, Beebe DW et al. Blood-based candidate biomarkers of the presence of neuropsychiatric systemic lupus erythematosus in children. Lupus Sci Med 2014; 1(1): e000038.
39. Yang X, Lin J Lu X, Zhao X. Expression of S100B protein levels in serum and cerebrospinal fluid with different forms of neuropsychiatric systemic lupus erythematosus. Clin Rheumatol 2008; 27(3): 353–7.
40. Is M, Coskun A, Sanus GZ, Tanriverdi T, Kafadar AM, Hanimoglu H, et al. High- sensitivity C-reactive protein levels in cerebrospinal fluid and serum in severe injury: Relationship to tumor necrosis factor and interleukin-6. J Clin Neurosci 2007; 14(12): 1163 –71.
41. Singhal A, Baker A, Hare G, Reinders FX, Schlichter LC, Moulton R. Association between cerebrospinal fluid interleukin-6 concentration and outcome after severe human traumatic brain injury. J Neurotrauma 2002; 8: 929–37.
42. Koudelková M, Sobek O, Kelbich P, Adam P, Melezinková V, Veselá B, Hajduková L, Adam D. Vyšetření cytokinů v likvoru. Labor Aktuell 2010; 01: 14–7.
43. Lipsky PE. Systemic lupus erythematosus: an autoimmune disease of B cell hyperactivity. Nat Immunol 2001; 2(9): 1615–6.
44. Jonsen A, Bengstsson AA, Nived O, Ryberg B, Truedsson L, Ronnblom L et al. The heterogenity of neuropsychiatric systemic lupus erythematosus is reflected in lack of association with cerebrospinal fluid profile. Lupus 2003; 12(11): 846–50.
45. Trysberg E, Carlsten H, Tarkowski A. Intrathecal cytokines in systemic lupus erythematosus with central nervous system involvement. Lupus 2000; 9(7): 498–503.
46. Santer DM,Yosio T, Minota S, Moller T, Elkon KB. Potent induction of INF-alpha and chemokines by autoantibodies in the cerebrospinal fluid of patients with neuropsychiatric lupus. J Immunol 2009; 182(2): 1192–1201.
47. Lu XY, Zhu CQ, Qian J, Chen XX, Ye A, Gu YY. Intrathecal cytokine and chemokine profiling in neuropsychiatric lupus or lupus complicated with central nervous system infection. Lupus 2010; 19(6): 689–695.
48. Dellalibera-Jovilino R et al. Cytokines in plasma and cerebrospinal fluid of patients with neuropsychiatric lupus. J Rheumatol 2003; 30(3): 485–492.
49. Kothur K, Wienholt L, Brilot F, Dale RC. CSF cytokines/chemokines as biomarkers in neuroinflammatory CNS disorders: A systematic review. Cytokine 2016; 77: 227–37.
50. Hirohata S, Miyamoto T. Elevated levels of interleukin-6 in systemic lupus erythematosus with central nervous system involvement. Arthritis Rheum 1990; 33: 644–9.
51. Fragoso-Loyo H, Richaud-Patin Y, Orozco-Narváez a et al. Interleukin-6 and chemokines in the neuropsychiatric manifestation of systemic lupus erythematosus. Arthritis Rheum 2007; 56: 1242–50.
52. Hirohata S, Kanai Y, Mitsuo A et al. Accuracy of cerebrospinal fluid IL-6 testing for diagnosis of lupus psychosis. A multicenter retrospective study. Clin Rheumatol 2009; 28: 1319–23.
53. Ishikawa A, Kurumi A, Hirohta S. Elevation of interleuin 8 in cerebrospinal fluid in neuropschiatric systemic lupus erythematosus. Kitasto Med J 2011; 41: 160–4.
54. Alcocer-Varela J, Aleman-Hoey D, Alarcon-Segovia D. Interleukin-1and interleukin-6 activities are increased in the cerebrospinal fluid of patients with CNS lupus erythematosus and correlated with local T-cell activation markers. Lupus 1992; 1: 111–7.
55. Fragoso-Loyo H, Atisha-Fregoso Y, Llorente L, Sanchez-Guerrero J. Inflammatory profile in cerebrospinal fluid of patients with headache as manifestation of neuropsychiatric systemic lupus erythematosus. Rheumatology 2013; 52: 2218–22.
56. Yoshio T, Okamoto H, Kurasawa K, Dei Y, Hirohata S, Minnota S. IL-6, IL-8, IP-10, MCP-1 and G-CSF are significantly increased in cerebrospinal fluid but not in sera patients with central neuropsychiatric lupus erythematosus. Lupus 2016; 25: 997–1003.
57. Lit LC, Wong CK, Tam LS, Li EK et al. Raised plasma concentration and ex vivo production of inflammatory chemokines in patients with systemic lupus erythematosus. Ann Rheum 2006; 65: 209–15.
58. Mok CC and Lau CS. Pathogenesis of systemic lupus erythematosus. J Clin Pathol 2003; 56: 481–90.
59. Okamoto H, Kobayashi A, Yamanaka H. Cytokines and chemokines in neuropsychiatric syndromes of systemic lupus erythematosus. J Biomed Biotechnol 2010; 268436.
60. Trysberg E, Blennow K, Zachrisson O, Tarkowski A. Intrathecal levels of matrix metalloproteinases in systemic lupus erythematosus with central nervous system involvement. Arthritis Res Ther 2004; 6: 551–6.
61. Ainiala H, Hietaharju P, Dastidar P, Loukkola J, Lehtimaki T, Peltola J, et al. Increased serum matrix metalloproteinase 9 levels in systemic lupus erythematosus patients with neuropsychiatric manifestation and brain magnetic resonance imaging abnormalities. Arthritis Rheum 2004; 50: 858–65.
62. Hanly JG. Diagnosis and management of neuropsychiatric SLE. Nat Rev Rheumatol 2014; 10: 338–47.
63. Hanly JG. New insights into central nervous system lupus: a clinical perspective. Curr Rheumatol Rep 2007; 9: 116–24.
64. Shiozawa S, Kuroki Y, Kim M, Hirohata S, Ogino T. Interferon-alpha in lupus psychosis. Arthritis Rheum 1992; 4: 417–22.
65. Fragoso-Loyo H, Atisha-Fregoso Y, Nunez-Alvarez CA et al. Utility of interferon alpha as a biomarker in central neuropsychiatric involvement in systemic lupus erythematosus. J Rheumatol 2012; 3: 504–9.
66. George-Chandy A, Trysberg E, Eriksson K. Raised intrathecal levels of APRIL and BAFF in patients with systemic lupus erythematosus: relationship to neuropsychiatric symptoms. Arthritis Res Ther 2008; 10(4): R97.
67. Ichinos K, Arima K, Ushigusa T, Nishino A, Nakashima Y, Suzuki T, et al. Distinguishing the cerebrospinal fluid cytokine profile in neuropsychiatric systemic lupus erythematosus from other autoimmune neurological diseases. Clinical Immunology 2015; 157: 114–20.
68. ShererY, Gorstein A, Fritzler MJ, Shoenfeld Y. Autoantibody explosion in systemic lupus erythematosus: more than 100 different antibodies found in SLE patients. Semin Arthritis Rheum 2004; 34: 501–37.
69. Zandman-Goddard G, Chapman J, Shoenfield Y. Autoantibodies involved in neuropsychiatric SLE and antiphospholipid syndrome. Semin Arthritis Rheum 2007; 36: 297–315.
70. Sciascia S, Bertolaccini LM, Roccatello D, Khamashta MA, Sanna G. Autoantibodies involved in neuropsychiatric manifestations associated with systemic lupus erythematosus: a systematic review. J Neurol 2014; 261: 1706–14.
71. Ho RC, Thiaghu C, Ong H, Lu Y, Ho CS, Tam WW, et al. A meta-analysis of serum and cerebrospinal fluid autoantibodies in neuropsychiatric systemic lupus erythematosus. Autoimmunity Rev2016; 15: 124–38.
72. Toubi E, Shoenfeld Y. Clinical and biological aspects of anti-P-ribosomal protein autoantibodies. Autoimmun Rev 2007; 6: 119–25.
73. Koren E, Reichlin MW, Wolfson-Reichlin M, Fugste RD, Trieu E, Targoff IN et al. Autoantibodies to the ribosomal P protein react with a plasma membrane-related target on human cells. J Clin Invest 1992; 89: 1236–41.
74. Stacey DW, Skelly S, Watson T, Elkon K et al. The inhibition of protein synthesis by IgG containing anti-ribosome P autoantibodies. Arch Biochem Biophys 1998; 267(1): 398–403.
75. Bravo-Zehnder M, Toledo EM, Segovia-Mirnda F, Serrano FG, Benito MJ, Metz C et al. Antiribosomal P protein autoantibodies from patients with neuropsychiatric lupus impact memory in mice. Arthritis Rheumatol Hob N J; 2015; 67: 204–14.
76. Matus S, Burgos PV, Bravo-Zehnder M, Kraft R, Porras OH et al. Antiribosomal P autoantibodies from psychiatric lupus target a novel neuronal surface protein causing calcium influx and apoptosis. J Exp Med 2007; 204: 3221–34.
77. Briani C, Lucchetta M, Ghirardello A, Toffanin E, Zampieri S, Ruggero S, Scarlato M et al. Neurolupus is associated with anti-ribosomal P protein antibodies: An inception cohort study. J Autoimmunity 2009; 32: 79–84.
78. Hirohata S, Arinuma Y, Takayama M, Yoshio T. Association of cerebrospinal fluid anti-ribosomal P protein antibodies with diffuse psychiatric/neuropsychological syndromes in systemic lupus erythematosus. Arthritis Res Ther 2007; 9: R44.
79. Bluestein HG, Williams GW, Steinberg AAD. Cerebrospinal fluid antibodies to neuronal cells: association with neuropsychiatric manifestation of systemic lupus erythematosus. Am J Med 1981; 70: 240–6.
80. Isshi K, Hirohata S. Differential roles of the anti-ribosomal P antibody and neuronal antibody in the pathogenesis of central nervous system involvement in systemic lupus erythematosus. Arthritis Rheum 1998; 41: 1819–27.
81. Lauvsnes MB, Omdal R. Systemic lupus erythematosus, the brain and anti-NR2 antibodies. J Neurol 2012; 259(4): 622–9.
82. Ozawa S, Kamiya H, Tsuzuki K. Glutamate receptors in the mammalian central nervous system.Prog Neurobiol 1998; 54(5): 581–618.
83. Barkus C, McHugh SB, Sprengel R, Seeburg PH, Rawlins JN, Bannerman DM. Hippocampal NMDA receptors and anxiety: at the interface between cognition and emotion. Eur J Pharmacol 2010; 626: 49–56.
84. Kowal C, DeGiorgio LA, Lee JY, Edgar MA et al. Human lupus antibodies against NMDA receptors mediate cognitive impairment. Proc Natl Acad Sci USA 2006; 103: 19854–9.
85. Kowal C, DeGiorgio LA, Nakaoka T, Hetherington H, Huerta PT, Diamond B et al. Cognition and immunity: antibody impairs memory. Immunity 2004; 21: 179–88.
86. Appenzeller S, Carnevalle AD, Li Lm, Costalllat LT, Cendes F. Hippocampal atrophy in systemic lupus erythematosus. Ann Rheum 2006; 65: 1585–9.
87. Lauvsnes MB, Beyer MK, Kvyloy JT, Greve OJ et al. Association of hippocampal atrophy with cerebrospinal fluid antibodies against the NR2 subtype of N-methyl-d-aspartate receptor in patients with systemic lupus erythematosus and patients with primary Sjogren's syndrome. Arthritis Rheum 2014; 66: 3387–94.
88. Arinuma Y, Yanagida T, Hirohata S. Association of cerebrospinal fluid anti-NR2 glutamate receptor antibodies with diffuse neuropsychiatric lupus erythematosus. Arthritis Rheum 2008; 58(4): 1130–5.
89. Yoshio T, Onda H, Nara H, Minota S. Association of IgG anti NR-2 glutamate receptor antibodies in cerebrospinal fluid with neuropsychiatric systemic lupus erythematosus. Arthritis Rheum 2006; 54(2): 675–678.
90. Yoshio T, Okamoto H, Hirohata S, Minota. IgG anti-NR2 glutamate receptor autoantibodies from patients with systemic lupus erythematosus active endothelial cells. Arthritis Rheum 2013; 65: 457–63.
91. Diamond B, Volpe BT. A model for lupus brain disease. Immunol Rev 2012; 248: 56–67.
92. Hirohata S, Arinuma Y, Yanagida, Yoshio T. Blood-brain barrier damages and intrathecal synthesis of anti-N-methyl-d-aspartate receptor NR2 antibodies in diffuse psychiatric/neuropsychological syndromes in systemic lupus erythematosus. Arthritis Res Ther 2014; 16: R77.
93. Faust TW, Chang EH, Koval C, Berlin R, Gazaryan IG, Bertini E et al. Neurotoxic lupus autoantibodies alter brain function through two distinct mechanisms. Proc Natl Acad Sci USA 2010; 107: 18569–74.
94. Winfield JB, Brunner CM, Koffler D. Serologic studies in patients with systemic lupus erythematosus and central nervous system dysfunction. Arthritis Rheum 1978; 21: 289–94.
95. Yasuma M, Takasai Y, Matsumoto K, Kodama A, Hashimoto H, Hirose S. Clinical significance of IgG anti-Sm antibodies in patients with systemic lupus erythematosus. J Rheumatol 1990; 17: 469–75.
96. Hirohata S, Kosaka M. Association of anti-Sm antibodies with organic brain syndrome secondary to systemic lupus erythematosus. Lancet 1994; 343: 796.
97. Okada J, Hamana T, Kondo H. Anti-U1RN antibody and aseptic meningitis in connective tissue disease. Scand J Rheumatol 2003; 32: 247 – 52.
98. Fujita Y, Fujii T, Nakashima R, Tanaka M, Mimori T. Aseptic meningitis in mixed connective tissue disease: cytokine and anti U1RNP antibodies in cerebrospinal fluids from two different cases. Mod Rheumatol 2008; 18: 184 – 8.
99. Herbst F, Artlich A, Neuhauser G, Gortner L, Diehl M, Riss J. MCTD in the differential diagnosis of cereberall ataxia. Klin Padiatr 2001; 213: 332–3.
100. Sato T, Fujii T, Yokoyama, Fujita Y, Imura Y, Yukawa N, et al. Anti-U1RNP antibodies in cerebrospinal fluid are associated with central neuropsychiatric manifestations in systemic lupus erythematosus and mixed connective tissue disease. Arthritis Rheum 2010; 62: 3730–40.
101. Wen J, Doerner J, Weidenheim K, Xia Y, Stock A, Michaelson JS, et al. TNF-like weak inducer of apoptosis promotes blood brain barrier disruption and increases neuronal cell death in MRL/lpr mice. J Autoimmu 2015; 60: 40–50.
102. Jacob A, Hack B, Chiang, Garci JGN, Quigg RJ, Alexander JJ. C5a alters blood-brain barrier integrity in experimental lupus. FASEB J 2010; 24: 1682–8.
103. EULAR recommendations for the management of systemic lupus erythematosus with neuropsychiatric manifestations: report of a task force of the EULAR standing committee for clinical affairs. Ann Rheum Dis 2010; 69(12): 2074–82.
Štítky
Dermatology & STDs Paediatric rheumatology RheumatologyČlánok vyšiel v časopise
Czech Rheumatology
2018 Číslo 1
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