Паранеопластическая эндокринопатия при болезни Кастлемана и POEMS-синдроме

POEMS-синдром (P – полинейропатия, O – органомегалия, E – эндокринопатия, M – моноклональная гаммапатия, S – изменения кожи), ассоциированный с болезнью Кастлемана, моноклональной гаммапатией неясного значения, симптоматическими гемобластозами, системным амилоидозом, системными аутоиммунными заболеваниями, – редкий паранеопластический синдром, характеризующийся развитием полинейропатии, органомегалии, эндокринопатии, моноклональной гаммапатии и изменений кожи. Медленное развитие и неспецифичность большинства клинических проявлений, недостаточная информированность врачей различных специальностей являются основными причинами позднего обращения за медицинской помощью и длительного, иногда многолетнего, диагностического поиска. Даже после установки диагноза применение современных методов иммуносупрессивной, иммуномодулирующей или противоопухолевой терапии существенно ограничивается сложностями таксономической рубрификации диагноза, отсутствием единых терапевтических подходов и связанными с этим нерешенными вопросами профилизации и лекарственного обеспечения больных. В статье представлен обзор основных сведений о патогенезе и клинических проявлениях POEMS-синдрома. На примере пациента с болезнью Кастлемана продемонстрированы сложности первичной диагностики POEMS- синдрома и проблемы междисциплинарного взаимодействия врачей различных специальностей. Проанализировано значение эндокринных нарушений в диагностике и планировании терапии.

1. Bardwick P.A., Zvaifler N.J., Gill G.N. et al. Plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, M protein, and skin changes. Medicine 1980;59(4):311–22.DOI: 10.1097/00005792-198007000-00006.

2. Crow R.S. Peripheral neuritis in myelomatosis. BMJ 1956;2(4996):802–4. DOI: 10.1136/bmj.2.4996.802.

3. Shimpo S., Nishitani H., Tsunematsu T. et al. Solitary plasmacytoma with polyneuritis and endocrine disturbances. Nippon Rinsho 1968;26:2444–56.

4. Saikawa S. On the etiology of “PEP syndrome (a peculiar progressive polyneuritis associated with pigmentation, edema, plasma cell dyscrasia)”. Med J Kagoshima Univ 1980;32:219–43.

5. Driedger H., Pruzanski W. Plasma cell neoplasia with peripheral polyneuropathy. Medicine 1980;59(4):301–10. DOI: 10.1097/00005792-198007000-00005.

6. Takatsuki K., Yodoi J., Uchiyama T. et al. Plasma cell dyscrasia with polyneuropathy and endocrine disorders. Review of 36 cases. Neurol Med 1977;7:483–93.

7. Nakanishi T., Sobue I., Toyokura Y. et al. The Crow–Fukase syndrome: a study of 102 cases in Japan. Neurology 1984; 34(6):712. DOI: 10.1212/wnl.34.6.712.

8. Пирадов М.А., Супонева Н.А., Гинзберг М.А. и др. POEMS-синдром: обзор литературы и описание клинических наблюдений. Журнал неврологии и психиатрии 2014;4:4–10.

9. Михайлов А.М., Бессмельцев С.С., Агеева Т.А. и др. Болезнь Кастлемана с развитием POEMS-синдрома: особенности клинической картины, структуры лимфатических узлов и костного мозга. Бюллетень сибирского отделения Российской академии наук 2013;(2):63–71.

10. Dispenzieri A. POEMS Syndrome: 2019 Update on diagnosis, risk-stratification, and management. Am J Hematol 2019; 94(7):812–27. DOI: 10.1002/ajh.25495.

11. Kang W.Y., Shen K.N., Duan M.H. et al. 14q32 translocations and 13q14 deletions are common cytogenetic abnormalities in POEMS syndrome. Eur J Haematol 2013;91(6):490–6. DOI: 10.1111/ejh.12189.

12. Bryce A.H., Ketterling R.P., Gertz M.A. et al. A novel report of cig-FISH and cytogenetics in POEMS syndrome. Am J Hematol 2008;83(11):840–1. DOI: 10.1002/ajh.21285.

13. Nagao Y., Mimura N., Takeda J. et al. Genetic and transcriptional landscape of plasma cells in POEMS syndrome. Leukemia 2019;33(7):1723–35. DOI: 10.1038/s41375-018-0348-x.

14. Soubrier M., Labauge P., Jouanel P. et al. Restricted use of lambda genes in POEMS syndrome. Haematologica 2004;89(4):ECR02.

15. Abe D., Nakaseko C., Takeuchi M. et al. Restrictive usage of monoclonal immunoglobulin λ light chain germline in POEMS syndrome. Blood 2008;112(3):836–9. DOI: 10.1182/blood-2007-12-126979.

16. Dispenzieri A. POEMS syndrome. Blood Rev 2007;21(6):285–99. DOI: 10.1016/j.blre.2007.07.004.

17. Soubrier M., Dubost JJ., Serre A.F. et al. Growth factors in POEMS syndrome: evidence for a marked increase in circulating vascular endothelial growth factor. Arth Rheumat 1997;40(4):786–7. DOI: 10.1002/art.1780400430.

18. Kanai K., Sawai S., Sogawa K. et al. Markedly upregulated serum interleukin- 12 as a novel biomarker in POEMS syndrome. Neurology 2012;79(6):575–82. DOI: 10.1212/wnl.0b013e318263c42b.

19. Gheradi R., Belec L., Soubrier M. et al. Overproduction of proinflammatory cytokines imbalanced by their antagonists in POEMS syndrome. Blood 1996;87(4): 1458–65. DOI: 10.1182/blood.v87.4.1458.bloodjournal8741458.

20. Watanabe O., Arimura K., Kitajima I. et al. Greatly raised vascular endothelial growth factor (VEGF) in POEMS syndrome. Lancet 1996;347(9002):702. DOI: 10.1016/s0140-6736(96)91261-1.

21. Soubrier M., Guillon R., Dubost J.J. et al. Arterial obliteration in POEMS syndrome: possible role of vascular endothelial growth factor. J Rheumatol 1998;25(4):813–15.

22. Watanabe O., Maruyama I., Arimura K. et al. Overproduction of vascular endothelial growth factor/vascular permeability factor is causative in Crow–Fukase (POEMS) syndrome. Muscle Nerve 1998;21(11):1390–7. DOI: 10.1002/(SICI)1097-4598(199811) 21:11<1390::AID-MUS5>3.0.CO;2-4.

23. Nishi J., Arimura K., Utsunomiy A. et al. Expression of vascular endothelial growth factor in sera and lymph nodes of the plasma cell type of Castleman’s disease. Br J Haematol 1999;104(3):482–5. DOI: 10.1046/j.1365-2141.1999.01208.x.

24. Soubrier M., Sauron C., Souweine B. et al. Growth factors and proinflammatory cytokines in the renal involvement of POEMS syndrome. Am J Kidney Dis 1999;34(4):633–8. DOI: 10.1016/s0272-6386(99)70386-0.

25. Niimi H., Arimura K., Jonosono M. et al. VEGF is causative for pulmonary hypertension in a patient with Crow–Fukase (POEMS) syndrome. Int Med 2000;39(12):1101–4. DOI: 10.2169/internalmedicine.39.1101.

26. Scarlato M., Previtali S.C., Carpo M. et al. Polyneuropathy in POEMS syndrome: role of angiogenic factors in the pathogenesis. Brain 2005;128(8):1911–20. DOI: 10.1093/brain/awh519.

27. Kuwabara S., Misawa S., Kanai K. et al. Autologous peripheral blood stem cell transplantation for POEMS syndrome. Neurology 2005;66(1):105–7. DOI: 10.1212/01.wnl.0000188757.38495.23.

28. Mineta M., Hatori M., Sano H. et al. Recurrent Crow–Fukase syndrome associated with increased serum levels of vascular endothelial growth factor: a case report and review of the literature. Tohoku J Exp Med 2006;210(3):269–77. DOI: 10.1620/tjem.210.269.

29. D’Souza A., Hayman S.R., Buadi F. et al. The utility of plasma vascular endothelial growth factor levels in the diagnosis and follow-up of patients with POEMS syndrome. Blood 2011;118(17):4663–5. DOI: 10.1182/blood-2011-06-362392.

30. Kanai K., Kuwabara S., Misawa S. et al. Failure of treatment with anti-VEGF monoclonal antibody for long-standing POEMS syndrome. Int Med 2007;46(6):311–3. DOI: 10.2169/internalmedicine.46.6246.

31. Straume O., Bergheim J., Ernst P. Bevacizumab therapy for POEMS syndrome. Blood 2006;107(12):4972–4. DOI: 10.1182/blood-2005-12-5045.

32. Dietrich P.Y., Duchosal M.A. Bevacizumab therapy before autologous stem-cell transplantation for POEMS syndrome. Annal Oncol 2007;19(3):595. DOI: 10.1093/annonc/mdm602.

33. Badros A., Porter N., Zimrin A. Bevacizumab therapy for POEMS syndrome. Blood 2005;106(3):1135. DOI: 10.1182/blood-2005-03-0910.

34. Ohwada C., Nakaseko C., Sakai S. et al. Successful combination treatment with bevacizumab, thalidomide and autologous PBSC for severe POEMS syndrome. Bone Marr Transplant 2008;43(9):739–40. DOI: 10.1038/bmt.2008.381.

35. Samaras P., Bauer S., Stenner-Liewen F. et al. Treatment of POEMS syndrome with bevacizumab. Haematologica 2007;92(10): 1438–9. DOI: 10.3324/haematol.11315.

36. Sekiguchi Y., Misawa S., Shibuya K. et al. Ambiguous effects of anti-VEGF monoclonal antibody (bevacizumab) for POEMS syndrome. J Neurol 2013;84(12):1346–8. DOI: 10.1136/jnnp-2012-304874.

37. Endo I., Mitsui T., Nishino M. et al. Diurnal fluctuation of edema synchronized with plasma VEGF concentration in a patient with POEMS syndrome. Int Med 2002;41(12):1196–8. DOI: 10.2169/internalmedicine.41.1196.

38. Nakano A., Mitsui T., Endo I. et al. Solitary plasmacytoma with VEGF overproduction: report of a patient with polyneuropathy. Neurology 2001; 56(6):818–9. DOI: 10.1212/wnl.56.6.818.

39. Koga H., Tokunaga Y., Hisamoto T. et al. Ratio of serum vascular endothelial growth factor to platelet count correlates with disease activity in a patient with POEMS syndrome. Eur J Int Med 2002;13(1):70–4. DOI: 10.1016/s0953-6205(01)00199-6.

40. Wang C., Huang X.F., Cai Q.Q. et al. Remarkable expression of vascular endothelial growth factor in bone marrow plasma cells of patients with POEMS syndrome. Leuk Res 2016;50:78–84. DOI: 10.1016/j.leukres.2016.09.017.

41. Lavenstain B., Dalakas M., Engel W.K. et al. Polyneuropathy in non-secretory osteosclerotic multiple myeloma with immunoglobulin deposition in peripheral nerve tissue. Neurology 1979;29:611.

42. Ghandi G.Y., Basu R., Dispenzieri A. et al. Endocrinopathy in POEMS syndrome: the Mayo clinic experience. Mayo Clinic Proc 2007 l;82(7):836–42. DOI: 10.4065/82.7.836.

43. Gherardi R., Baudrimont M., Kujas M. et al. Pathological findings in three non- japanese patients with the POEMS syndrome. Virch Arch Pathol Anat Histopathol 1988;413(4):357–66. DOI: 10.1007/bf00783029.

44. Allam J.S., Kennedy C.C., Aksamit T.R. et al. Pulmonary manifestations in patients with POEMS syndrome. Chest 2008;133(4):969–74. DOI: 10.1378/chest.07-1800.

45. Barete S., Mouawad R., Choquet S. et al. Skin manifestations and vascular endothelial growth factor levels in POEMS syndrome. Arch Dermatol 2010;146(6). DOI: 10.1001/archdermatol.2010.100.

46. Distler O., Del Rosso A., Giacomelli R. et al. Angiogenic and angiostatic factors in systemic sclerosis: increased levels of vascular endothelial growth factor are a feature of the earliest disease stages and are associated with the absence of fingertip ulcers. Arths Res 2002;4(6):R11. DOI: 10.1186/ar596.

47. Miest R.Y.N., Comfere N.I., Dispenzieri A. et al. Cutaneous manifestations in patients with POEMS syndrome. Int J Dermatol 2013;52(11):1349–56. DOI: 10.1111/j.1365-4632.2012.05648.x.

48. Dispenzieri A. POEMS syndrome: update on diagnosis, risk-stratification, and management. Am J Hematology 2012;87:805–14.

49. Miralles G.D., O’Fallon J.R., Talley N.J. Plasma-cell dyscrasia with polyneuropathy. New Eng J Med 1992;327(27):1919–23. DOI: 10.1056/nejm199212313272705.

50. Dispenzieri A., Buadi F.K. A review of POEMS syndrome. Cancer Network, 2013. Pp. 1–11.

51. Wang Y., Huang L., Shi Y. et al. Characteristics of 1946 Cases of POEMS syndrome in chinese subjects: a literaturebased study. Front Immunol 2019;10. DOI: 10.3389/fimmu.2019.01428.

52. Dispenzieri A., Kyle R.A., Lacy M.Q. et al. POEMS syndrome: definitions and long-term outcome. Blood 2003;101(7):2496–506. DOI: 10.1182/blood-2002-07-2299.

53. Li J., Zhou D.B., Huang Z. et al. Clinical characteristics and long-term outcome of patients with POEMS syndrome in China. Annal Hematol 2011;90(7):819–26. DOI: 10.1007/s00277-010-1149-0.

54. Kaushik M., Pulido J.S., Abreu R. et al. Ocular findings in patients with polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes syndrome. Ophthalmology 2011;118(4):778–82. DOI: 10.1016/j.ophtha.2010.08.013.

55. Mizuiri S., Mitsuo K., Sakai K. et al. Renal involvement in POEMS syndrome. Nephron 1991;59(1):153–6. DOI: 10.1159/000186536.

56. Nakamoto Y., Imai H., Yasuda T. et al. A spectrum of clinicopathological features of nephropathy associated with POEMS syndrome. Nephrol Dialys Transplant 1999;14(10):2370–86. DOI: 10.1093/ndt/14.10.2370.

57. Dispenzieri A. Castleman disease. Rare Hematological Malignancies Springer US. Pp. 293–330. Available at: http://dx.doi.org/10.1007/978-0-387-73744-7_13.

58. Yu L., Tu M., Cortes J. et al. Clinical and pathological characteristics of HIV- and HHV-8-negative Castleman disease. Blood 2017;129(12):1658–68. DOI: 10.1182/blood-2016-11-748855.

59. Li H., Huang Y., Li Y. et al. Endocrine manifestations in POEMS syndrome: a case report and literature review. BMC Endocr Disord 2019;19(1):33. DOI: 10.1186/s12902-019-0355-6.

60. Caimari F., Keddie S., Lunn M.P. et al. Prevalence and course of endocrinopathy in POEMS syndrome. J Clin Endocrinol Metabol 2018;104(6):2140–6. DOI: 10.1210/jc.2018-01516.

61. Lewandowski K., Al-Din A., Spencer N. et al. Addisonian crisis in a patient with a progressive polyneuropathy. Endocr Abstr 2003;5:19. Available at: https://www.endocrine-abstracts.org/ea/0005/ea0005p19.

62. Prokop J., Estorninho J., Marote S. et al. POEMS syndrome: a rare cause of adrenal insufficiency in a young male. Endocrinol Diabet Metabol Case Rep 2019. DOI: 10.1530/EDM-19-0010.

63. Bruno C., Fleck J., Cavaghan M. Pituitary macroadenoma in a patient with poems syndrome in conjunction with Castleman disease: first report of a case and review of related literature. Endocr Pract 2010;16(1):97–101. DOI: 10.4158/ep09027.crr.

64. Rajkumar S., Dimopoulos M.A., Palumbo A. et al. Interntional Myeloma Working Group updated criteria for the diagnosis of multiple myeloma. Lancet Oncology 2014:15(12):538–48. DOI: 10.1016/S1470-2045(14)70442-5.

65. Dao L.N., Hanson C.A., Dispenzieri A. et al. Bone marrow histopathology in POEMS syndrome: a distinctive combination of plasma cell, lymphoid, and myeloid findings in 87 patients. Blood 2011;117(24):6438–44. DOI: 10.1182/blood-2010-11-316935.