Болезнь Эрдгейма-Честера (ЭЧБ) является редким заболеванием, относится к нелангергансовым гистиоцитозам неизвестной этиологии, характеризуется ксантогранулематозной инфильтрацией различных тканей пенистыми гистиоцитами классов CD68+, CD1a-, S-100- (1,2).
Потенциально ЭЧБ может развиться в любом органе или ткани. Клиника зависит от длительности развития и распространенности патологических очагов, может варьировать от бессимптомного поражения костной ткани до мультисистемных форм, угрожающих жизни (3).
Диагностика этого заболевания затруднена, общий прогноз неблагоприятен. В последние годы применяются новые патогенетические подходы к лечению ЭЧБ с применением биологически активных веществ и ингибиторов BRAF. В статье мы обсудим основы ЭЧБ, начиная с этиопатогенеза, и заканчивая современными подходами к лечению.
Эпидемиология
ЭЧБ является весьма редким заболеванием, и зачастую упускается. С момента первого описания учеником Якоба Эрдгейма, Вильямом Честером в 1930 году (4), было выявлено более 500 случаев заболевания. В последние годы число вновь диагностируемых случаев существенно выросло из-за повышенного внимания медицинского сообщества.
ЭЧБ чаще встречается у мужчин (соотношение мужчины:женщины составляет 1,5), различия в клинике заболевания между полами отсутствуют (3). Наиболее часто болезнь поражает мужчин среднего возраста (медиана возраста пациентов с впервые поставленным диагнозом составляет 53 года)(3). ЭЧБ редко развивается у детей, описаны только несколько случаев (5,6).
1. Haroche J, Arnaud L, Amoura Z. Erdheim – Chester disease. 2012;53–9.
2. Veyssier-Belot C, Cacoub P, Caparros-Lefebvre D, Wechsler J, Brun B, Remy M, et al. Erdheim-Chester disease. Clinical and radiologic characteristics of 59 cases. Medicine (Baltimore). 1996 May;75(3):157–69.
3. Cavalli G, Guglielmi B, Berti A, Campochiaro C, Sabbadini MG, Dagna L. The multifaceted clinical presentations and manifestations of Erdheim-Chester disease: comprehensive review of the literature and of 10 new cases. Annals of the rheumatic diseases. 2013. p. 1691–5.
4. Chester W. Uber Lipoidgranulomatose 1. Virchows Arch für Pathol Anat und Physiol und für Klin Medizin. 1930;279:561–602.
5. Jeon I, Lee SS, Lee MK. Chemotherapy and interferon-alpha treatment of Erdheim-Chester disease. Pediatr Blood Cancer. 2010 Oct;55(4):745–7.
6. Tran T-A, Fabre M, Pariente D, Craiu I, Haroche J, Charlotte F, et al. Erdheim-Chester disease in childhood: a challenging diagnosis and treatment. J Pediatr Hematol Oncol. 2009 Oct;31(10):782–6.
7. Haroche J, Arnaud L, Cohen-Aubart F, Hervier B, Charlotte F, Emile JF, et al. Erdheim-chester disease. Rheumatic Disease Clinics of North America. 2013. p. 299–311.
8. Bancroft LW, Berquist TH. Erdheim-Chester disease: radiographic findings in five patients. Skeletal Radiol. 1998 Mar;27(3):127–32.
9. Dion E, Graef C, Miquel A, Haroche J, Wechsler B, Amoura Z, et al. Bone involvement in Erdheim-Chester disease: imaging findings including periostitis and partial epiphyseal involvement. Radiology. 2006 Feb;238(2):632–9.
10. Balink H, Hemmelder MH, de Graaf W, Grond J. Scintigraphic diagnosis of Erdheim-Chester disease. J Clin Oncol. 2011 Jun 1;29(16):e470–2.
11. Kujat C, Martin J, Püschel W. [Erdheim-Chester disease]. Radiologe. 1991 Jun;31(6):297–306.
12. Arnaud L, Hervier B, Néel A, Hamidou M a, Kahn J-E, Wechsler B, et al. CNS involvement and treatment with interferon-α are independent prognostic factors in Erdheim-Chester disease: a multicenter survival analysis of 53 patients. Blood. 2011 Mar 10;117(10):2778–82.
13. Lachenal F, Cotton F, Desmurs-Clavel H, Haroche J, Taillia H, Magy N, et al. Neurological manifestations and neuroradiological presentation of Erdheim-Chester disease: report of 6 cases and systematic review of the literature. J Neurol. 2006 Oct;253(10):1267–77.
14. Drier A, Haroche J, Savatovsky J, Godenèche G, Dormont D, Chiras J, et al. Cerebral, facial, and orbital involvement in Erdheim-Chester disease: CT and MR imaging findings. Radiology. 2010 May;255(2):586–94.
15. Sheu S-Y, Wenzel RR, Kersting C, Merten R, Otterbach F, Schmid KW. Erdheim-Chester disease: case report with multisystemic manifestations including testes, thyroid, and lymph nodes, and a review of literature. J Clin Pathol. 2004 Nov;57(11):1225–8.
16. Khamseh ME, Mollanai S, Hashemi F, Rezaizadeh A, Azizi F. Erdheim-Chester syndrome, presenting as hypogonadotropic hypogonadism and diabetes insipidus. J Endocrinol Invest. 2002 Sep;25(8):727–9.
17. Kovacs K, Bilbao JM, Fornasier VL, Horvath E. Pituitary pathology in Erdheim-Chester disease. Endocr Pathol. 2004 Jan;15(2):159–66.
18. Tritos NA, Weinrib S, Kaye TB. Endocrine manifestations of Erdheim-Chester disease (a distinct form of histiocytosis). J Intern Med. 1998 Dec;244(6):529–35.
19. Haroche J, Amoura Z, Touraine P, Seilhean D, Graef C, Birmelé B, et al. Bilateral adrenal infiltration in Erdheim-Chester disease. Report of seven cases and literature review. J Clin Endocrinol Metab. 2007 Jun;92(6):2007–12.
20. Droupy S, Attias D, Eschwege P, Hammoudi Y, Benoit G, Jardin A. Bilateral hydronephrosis in a patient with Erdheim-Chester disease. J Urol. 1999 Dec;162(6):2084–5.
21. Verdalles U, Goicoechea M, García de Vinuesa S, Mosse A, Luño J. Erdheim-Chester disease: a rare cause of renal failure. Nephrol Dial Transplant. 2007 Jun;22(6):1776–7.
22. Sanchez JE, Mora C, Macia M, Navarro JF. Erdheim-Chester disease as cause of end-stage renal failure: a case report and review of the literature. Int Urol Nephrol. 2010 Dec;42(4):1107–12.
23. Bangard C, Lotz J, Rosenthal H, Galanski M. Erdheim-Chester disease versus multifocal fibrosis and Ormond’s disease: a diagnostic dilemma. Clin Radiol. 2004 Dec;59(12):1136–41.
24. Haroche J, Amoura Z, Dion E, Wechsler B, Costedoat-chalumeau N, Cacoub P, et al. Cardiovascular Involvement , an Overlooked Feature Report of 6 New Cases and a Literature Review. 2004;83(6):371–92.
25. Dion E, Graef C, Haroche J, Renard-Penna R, Cluzel P, Wechsler B, et al. Imaging of thoracoabdominal involvement in Erdheim-Chester disease. AJR Am J Roentgenol. 2004 Nov;183(5):1253–60.
26. Arnaud L, Pierre I, Beigelman-Aubry C, Capron F, Brun A-L, Rigolet A, et al. Pulmonary involvement in Erdheim-Chester disease: a single-center study of thirty-four patients and a review of the literature. Arthritis Rheum. 2010 Nov;62(11):3504–12.
27. Kambouchner M, Colby T V, Domenge C, Battesti JP, Soler P, Tazi A. Erdheim-Chester disease with prominent pulmonary involvement associated with eosinophilic granuloma of mandibular bone. Histopathology. 1997 Apr;30(4):353–8.
28. Egan AJ, Boardman LA, Tazelaar HD, Swensen SJ, Jett JR, Yousem SA, et al. Erdheim-Chester disease: clinical, radiologic, and histopathologic findings in five patients with interstitial lung disease. Am J Surg Pathol. 1999 Jan;23(1):17–26.
29. Madroszyk A, Wallaert B, Rémy M, Rémy J, Gosselin B, Caparros D, et al. [Diffuse interstitial pneumonia revealing Erdheim-Chester’s disease]. Rev Mal Respir. 1994 Jan;11(3):304–7.
30. Brun A-L, Touitou-Gottenberg D, Haroche J, Toledano D, Cluzel P, Beigelman-Aubry C, et al. Erdheim-Chester disease: CT findings of thoracic involvement. Eur Radiol. 2010 Nov;20(11):2579–87.
31. George OK, Subhendu MSK. Recurrent and rapidly occurring pericardial tamponade in Erdheim Chester disease. Indian Heart J. 64(1):103–5.
32. Gupta A, Kelly B, McGuigan JE. Erdheim-Chester disease with prominent pericardial involvement: clinical, radiologic, and histologic findings. Am J Med Sci. 2002 Aug;324(2):96–100.
33. Haroche J, Cluzel P, Toledano D, Montalescot G, Touitou D, Grenier PA, et al. Images in cardiovascular medicine. Cardiac involvement in Erdheim-Chester disease: magnetic resonance and computed tomographic scan imaging in a monocentric series of 37 patients. Circulation. 2009 Jun 30;119(25):e597–8.
34. Merli E, Savelli F, Lovato L, Zompatori M. Cardiac involvement in Erdheim-Chester disease: echocardiographic appearance and value of cardiac MRI. Eur Heart J Cardiovasc Imaging. 2012 Feb;13(2):198.
35. Serratrice J, Granel B, De Roux C, Pellissier JF, Swiader L, Bartoli JM, et al. “Coated aorta”: a new sign of Erdheim-Chester disease. J Rheumatol. 2000 Jun;27(6):1550–3.
36. Fink MG, Levinson DJ, Brown NL, Sreekanth S, Sobel GW. Erdheim-Chester disease. Case report with autopsy findings. Arch Pathol Lab Med. 1991 Jun;115(6):619–23.
37. Loeffler AG, Memoli VA. Myocardial involvement in Erdheim-Chester disease. Arch Pathol Lab Med. 2004 Jun;128(6):682–5.
38. Vaideeswar P, Vaz WF. Erdheim-Chester disease with extensive coronary arterial involvement. Pathology. 2011 Jun;43(4):375–8.
39. Cavalli G, Berti A, Campochiaro C, Dagna L. Diagnosing Erdheim-Chester disease. Ann Rheum Dis. 2013 Jul;72(7):e19.
40. Haroche J, Arnaud L, Cohen-Aubart F, Hervier B, Charlotte F, Emile J-F, et al. Erdheim-Chester disease. Rheum Dis Clin North Am. 2013 May;39(2):299–311.
41. Tsai J-W, Tsou J-H, Hung L-Y, Wu H-B, Chang K-C. Combined Erdheim-Chester disease and Langerhans cell histiocytosis of skin are both monoclonal: a rare case with human androgen-receptor gene analysis. J Am Acad Dermatol. 2010 Aug;63(2):284–91.
42. Yin J, Zhang F, Zhang H, Shen L, Li Q, Hu S, et al. Hand-Schüller-Christian disease and Erdheim-Chester disease: coexistence and discrepancy. Oncologist. 2013 Jan;18(1):19–24.
43. Wang K-H, Cheng C-J, Hu C-H, Lee W-R. Coexistence of localized Langerhans cell histiocytosis and cutaneous Rosai-Dorfman disease. Br J Dermatol. 2002 Oct;147(4):770–4.
44. Devouassoux G, Lantuejoul S, Chatelain P, Brambilla E, Brambilla C. Erdheim-Chester Disease. 1998;
45. Chetritt J, Paradis V, Dargere D, Adle-Biassehe H, Maurage CA, Mussini JM, et al. Chester-Erdheim disease: A neoplastic disorder. Hum Pathol. 1999;30:1093–6.
46. Al-Quran S, Reith J, Bradley J, Rimsza L. Erdheim-Chester disease: case report, PCR-based analysis of clonality, and review of literature. Mod Pathol. 2002 Jun;15(6):666–72.
47. Vencio EF, Jenkins RB, Schiller JL, Huynh TVT, Wenger DD, Inwards CY, et al. Clonal cytogenetic abnormalities in Erdheim-Chester disease. The American journal of surgical pathology. 2007. p. 319–21.
48. Stoppacciaro A, Ferrarini M, Salmaggi C, Colarossi C, Praderio L, Tresoldi M, et al. Immunohistochemical evidence of a cytokine and chemokine network in three patients with Erdheim-Chester disease: implications for pathogenesis. Arthritis Rheum. 2006;54:4018–22.
49. Arnaud L, Gorochov G, Charlotte F, Lvovschi V, Parizot C, Larsen M, et al. Systemic perturbation of cytokine and chemokine networks in Erdheim-Chester disease: a single-center series of 37 patients. Blood. 2011 Mar 10;117(10):2783–90.
50. Ferrero E, Belloni D, Corti A, Doglioni C, Dagna L, Ferrarini M. TNF-α in Erdheim-Chester disease pericardial effusion promotes endothelial leakage in vitro and is neutralized by infliximab. Rheumatology (Oxford). 2014 Jan;53(1):198–200.
51. Aouba A, Georgin-Lavialle S, Pagnoux C, Martin Silva N, Renand A, Galateau-Salle F, et al. Rationale and efficacy of interleukin-1 targeting in Erdheim-Chester disease. Blood. 2010 Nov 18;116(20):4070–6.
52. Dagna L, Corti A, Langheim S, Guglielmi B, De Cobelli F, Doglioni C, et al. Tumor necrosis factor α as a master regulator of inflammation in Erdheim-Chester disease: rationale for the treatment of patients with infliximab. J Clin Oncol. 2012 Oct 1;30(28):e286–90.
53. Courcoul A, Vignot E, Chapurlat R. Successful treatment of Erdheim-Chester disease by interleukin-1 receptor antagonist protein. Joint Bone Spine. 2013 Aug 13;
54. Killu AM, Liang JJ, Jaffe AS. Erdheim-Chester disease with cardiac involvement successfully treated with anakinra. Int J Cardiol. 2013 Sep 1;167(5):e115–7.
55. Aubert O, Aouba A, Deshayes S, Georgin-Lavialle S, Rieu P, Hermine O. Favorable radiological outcome of skeletal Erdheim-Chester disease involvement with anakinra. Joint Bone Spine. 2013 Mar;80(2):206–7.
56. Blombery P, Wong SQ, Lade S, Prince HM. Erdheim-Chester disease harboring the BRAF V600E mutation. J Clin Oncol. 2012 Nov 10;30(32):e331–2.
57. Haroche J, Charlotte F, Arnaud L, von Deimling A, Hélias-Rodzewicz Z, Hervier B, et al. High prevalence of BRAF V600E mutations in Erdheim-Chester disease but not in other non-Langerhans cell histiocytoses. Blood. 2012 Sep 27;120(13):2700–3.
58. Emile J-F, Charlotte F, Amoura Z, Haroche J. BRAF mutations in Erdheim-Chester disease. J Clin Oncol. 2013 Jan 20;31(3):398.
59. Badalian-Very G, Vergilio J-A, Degar B a, MacConaill LE, Brandner B, Calicchio ML, et al. Recurrent BRAF mutations in Langerhans cell histiocytosis. Blood. 2010 Sep 16;116(11):1919–23.
60. Satoh T, Smith A, Sarde A, Lu H, Mian S, Trouillet C, et al. B-RAF Mutant Alleles Associated with Langerhans Cell Histiocytosis , a Granulomatous Pediatric Disease. 2012;7(4).
61. Capper D, Preusser M, Habel A, Sahm F. Assessment of BRAF V600E mutation status by immunohistochemistry with a mutation-specific monoclonal antibody. 2011;600:11–9.
62. Sahm F, Capper D, Preusser M, Meyer J, Stenzinger A, Lasitschka F, et al. BRAFV600E mutant protein is expressed in cells of variable maturation in Langerhans cell histiocytosis. Blood. 2012 Sep 20;120(12):e28–34.
63. Cangi MG, Biavasco R, Cavalli G, Grassini G, Dal-cin E, Campochiaro C, et al. BRAF V600E -mutation is invariably present and associated to oncogene-induced senescence in Erdheim-Chester disease. Ann Rheum Dis. 2014;1–7.
64. Sebolt-Leopold JS, Herrera R. Targeting the mitogen-activated protein kinase cascade to treat cancer. Nat Rev Cancer. 2004 Dec;4(12):937–47.
65. Li Y, Nakamura M, Kakudo K. Targeting of the BRAF gene in papillary thyroid carcinoma (review). Oncol Rep. 2009 Oct;22(4):671–81.
66. Tiacci E, Trifonov V, Schiavoni G, Holmes A, Kern W, Martelli MP, et al. BRAF mutations in hairy-cell leukemia. N Engl J Med. 2011 Jun 16;364(24):2305–15.
67. Wellbrock C, Hurlstone A. BRAF as therapeutic target in melanoma. Biochem Pharmacol. 2010 Sep 1;80(5):561–7.
68. Kuilman T, Michaloglou C, Vredeveld LCW, Douma S, Doorn R Van, Desmet CJ, et al. Oncogene-Induced Senescence Relayed by an Interleukin-Dependent Inflammatory Network. 2008;1019–31.
69. Michaloglou C, Vredeveld LCW, Soengas MS, Denoyelle C, Kuilman T, van der Horst CMAM, et al. BRAFE600-associated senescence-like cell cycle arrest of human naevi. Nature. 2005 Aug 4;436(7051):720–4.
70. Haroche J, Cohen-aubart F, Emile J, Arnaud L, Maksud P. Dramatic efficacy of vemurafenib in both multisystemic and refractory Erdheim-Chester disease and Langerhans cell histiocytosis harboring the BRAF V600E mutation. 2013;
71. Myra C, Sloper L, Tighe PJ, McIntosh RS, Stevens SE, Gregson RHS, et al. Treatment of Erdheim-Chester disease with cladribine: a rational approach. Br J Ophthalmol. 2004 Jun;88(6):844–7.
72. Boissel N, Wechsler B, Leblond V. Treatment of refractory Erdheim-Chester disease with double autologous hematopoietic stem-cell transplantation. Ann Intern Med. 2001 Nov 6;135(9):844–5.
73. Gaspar N, Boudou P, Haroche J, Wechsler B, Van Den Neste E, Hoang-Xuan K, et al. High-dose chemotherapy followed by autologous hematopoietic stem cell transplantation for adult histiocytic disorders with central nervous system involvement. Haematologica. 2006 Aug;91(8):1121–5.
74. Braiteh F, Boxrud C, Esmaeli B, Kurzrock R. Successful treatment of Erdheim-Chester disease, a non-Langerhans-cell histiocytosis, with interferon-alpha. Blood. 2005 Nov 1;106(9):2992–4.
75. Haroche J, Amoura Z, Trad SG, Wechsler B, Cluzel P, Grenier PA, et al. Variability in the Efficacy of Interferon-a in Erdheim-Chester Disease by Patient and Site of Involvement Results in Eight Patients. 2006;54(10):3330–6.
76. Janku F, Amin HM, Yang D, Garrido-Laguna I, Trent JC, Kurzrock R. Response of histiocytoses to imatinib mesylate: fire to ashes. J Clin Oncol. 2010 Nov 1;28(31):e633–6.
77. Dietrich S, Glimm H, Andrulis M, von Kalle C, Ho AD, Zenz T. BRAF inhibition in refractory hairy-cell leukemia. N Engl J Med. 2012 May 24;366(21):2038–40.
78. Haroche J, Cohen-Aubart F, Emile J-F, Arnaud L, Maksud P, Charlotte F, et al. Dramatic efficacy of vemurafenib in both multisystemic and refractory Erdheim-Chester disease and Langerhans cell histiocytosis harboring the BRAF V600E mutation. Blood. 2013;121:1495–500.
79. Belum VR, Fischer A, Choi JN, Lacouture ME. Dermatological adverse events from BRAF inhibitors: a growing problem. Curr Oncol Rep. 2013 Jun;15(3):249–59.
80. Callahan MK, Rampal R, Harding JJ, Klimek VM, Chung YR, Merghoub T, et al. Progression of RAS-mutant leukemia during RAF inhibitor treatment. N Engl J Med. 2012 Dec 13;367(24):2316–21.
81. Arnaud L, Malek Z, Archambaud F, Kas A, Toledano D, Drier A, et al. 18F-fluorodeoxyglucose-positron emission tomography scanning is more useful in followup than in the initial assessment of patients with Erdheim-Chester disease. Arthritis Rheum. 2009 Oct;60(10):3128–38.
Вся информация, размещенная на данном веб-сайте, предназначена исключительно для специалистов здравоохранения — медицинских и фармацевтических работников.
*Если Вы не являетесь специалистом здравоохранения, в соответствии с положениями действующего законодательства РФ Вы не имеете права доступа к информации, размещенной на данном веб-сайте.
