Clinical considerations and key issues in the management of patients with Erdheim-Chester Disease: a seven case series

BMC Medicine

Yehuda Shoenfeld⁸  Chezi Ganzel¹  Alexander Gural⁷  Iris Yaish⁹  Eli Sprecher^1,10  Ilan Goldberg^1,10  Yakov Pessach^1,10  Ronald Jaffe⁶  Iris Eshed⁴  Orna Aizenstein⁵  Anat Kesler³  Mirra Manevich-Mazor²  Roei D Mazor² 

[1] Department of Hematology, Shaare Zedek Medical Center, Jerusalem, Israel;Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel;Department of Ophthalmology, Neuro-ophthalmology Unit, Tel Aviv-Sourasky Medical Center, Tel Aviv, Israel;Department of Diagnostic Imaging, Sheba Medical Center, Tel Aviv University, Tel Hashomer, Israel;Department of Radiology, Neuroradiology Unit, Tel Aviv-Sourasky Medical Center, Tel Aviv, Israel;Department of Pathology, University of Pittsburgh, School of Medicine and Children’s Hospital, Pittsburgh, USA;Department of Hematology, Hadassah University Hospital, Jerusalem, Israel;The Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Tel Hashomer, Israel;Institute of Endocrinology, Metabolism and Hypertension, Tel Aviv-Sourasky Medical Center, Tel Aviv, Israel;Department of Dermatology, Tel-Aviv Sourasky Medical Center, Tel-Aviv, Israel

关键词: Histiocytosis;    Interferon-α;    Vemurafenib;    NRAS;    BRAF;    Erdheim Chester;   

Others  :  1118130
DOI  :  10.1186/s12916-014-0221-3

 received in 2014-08-18, accepted in 2014-11-03,  发布年份 2014

【 摘 要 】

Background

Erdheim-Chester Disease (ECD), a non Langerhans’ cell histiocytosis of orphan nature and propensity for multi-systemic presentations, comprises an intricate medical challenge in terms of diagnosis, treatment and complication management.

Objectives

The objectives are to report the clinical, radiological and pathological characteristics, as well as cardinal therapeutic approaches to ECD patients and to provide clinical analyses of the medical chronicles of these complex patients.

Methods

Patients with biopsy proven ECD were audited by a multi-disciplinary team of specialists who formed a coherent timeline of all the substantial clinical events in the evolution of their patients’ illness.

Results

Seven patients (five men, two women) were recruited to the study. The median age at presentation was 53 years (range: 39 to 62 years). The median follow-up time was 36 months (range: 1 to 72 months). Notable ECD involvement sites included the skeleton (seven), pituitary gland (seven), retroperitoneum (five), central nervous system (four), skin (four), lungs and pleura (four), orbits (three), heart and great vessels (three) and retinae (one). Prominent signs and symptoms were fever (seven), polyuria and polydipsia (six), ataxia and dysarthria (four), bone pain (four), exophthalmos (three), renovascular hypertension (one) and dyspnea (one). The V600E BRAF mutation was verified in three of six patients tested. Interferon-α treatment was beneficial in three of six patients treated. Vemurafenib yielded dramatic neurological improvement in a BRAF mutated patient. Infliximab facilitated pericardial effusion volume reduction. Cladribine improved cerebral blood flow originally compromised by perivenous lesions.

Conclusions

ECD is a complex, multi-systemic, clonal entity coalescing both neoplastic and inflammatory elements and strongly dependent on impaired RAS/RAF/MEK/ERK signaling.

【 授权许可】

   
2014 Mazor et al.; licensee BioMed Central Ltd.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

Figure 3.

Figure 4.

Figure 5.

Figure 6.

Figure 7.

Figure 8.

【 参考文献 】

• [1]Mazor RD, Manevich-Mazor M, Shoenfeld Y: Erdheim-Chester Disease: a comprehensive review of the literature. Orphanet J Rare Dis 2013, 8:137. BioMed Central Full Text
• [2]Munoz J, Janku F, Cohen PR, Kurzrock R: Erdheim-Chester disease: characteristics and management. Mayo Clin Proc 2014, 89:985-996.
• [3]Allen CE, McClain KL: Erdheim-Chester: beyond the lesion. Blood 2011, 117:2745-2746.
• [4]Wilejto M, Abla O: Langerhans cell histiocytosis and Erdheim-Chester disease. Curr Opin Rheumatol 2012, 24:90-96.
• [5]Haroche J, Arnaud L, Amoura Z: Erdheim-Chester disease. Curr Opin Rheumatol 2012, 24:53-59.
• [6]Dion E, Graef C, Miquel A, Haroche J, Wechsler B, Amoura Z, Zeitoun D, Grenier PA, Piette JC, Laredo JD: Bone involvement in Erdheim-Chester disease: imaging findings including periostitis and partial epiphyseal involvement. Radiology 2006, 238:632-639.
• [7]Drier A, Haroche J, Savatovsky J, Godeneche G, Dormont D, Chiras J, Amoura Z, Bonneville F: Cerebral, facial, and orbital involvement in Erdheim-Chester disease: CT and MR imaging findings. Radiology 2010, 255:586-594.
• [8]Oweity T, Scheithauer BW, Ching HS, Lei C, Wong KP: Multiple system Erdheim-Chester disease with massive hypothalamic-sellar involvement and hypopituitarism. J Neurosurg 2002, 96:344-351.
• [9]Carpinteri R, Patelli I, Casanueva FF, Giustina A: Pituitary tumours: inflammatory and granulomatous expansive lesions of the pituitary. Best Pract Res Clin Endocrinol Metab 2009, 23:639-650.
• [10]Vital C, Bioulac-Sage P, Tison F, Rivel J, Begueret H, Gomez C, Leaute-Labreze C, Diard F, Vital A: Brain stem infiltration by mixed Langerhans cell histiocytosis and Chester-Erdheim disease: more than just an isolated case? Clin Exp Pathol 1999, 47:71-76.
• [11]Sedrak P, Ketonen L, Hou P, Guha-Thakurta N, Williams MD, Kurzrock R, Debnam JM: Erdheim-Chester disease of the central nervous system: new manifestations of a rare disease. AJNR Am J Neuroradiol 2011, 32:2126-2131.
• [12]Haroche J, Cluzel P, Toledano D, Montalescot G, Touitou D, Grenier PA, Piette JC, Amoura Z: 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, 119:e597-e598.
• [13]Killu AM, Liang JJ, Jaffe AS: Erdheim-Chester disease with cardiac involvement successfully treated with anakinra. Int J Cardiol 2013, 167:e115-117.
• [14]Monti L, Haroche J, Sciarra A, Balzarini L, Fiamengo B, Amoura Z, Graziani G: Interferon-alpha in cardiac Erdheim-Chester disease. J Am Coll Cardiol 2011, 58:2695.
• [15]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, 13:198.
• [16]Arnaud L, Pierre I, Beigelman-Aubry C, Capron F, Brun AL, Rigolet A, Girerd X, Weber N, Piette JC, Grenier PA, Amoura Z, Haroche J: Pulmonary involvement in Erdheim-Chester disease: a single-center study of thirty-four patients and a review of the literature. Arthritis Rheum 2010, 62:3504-3512.
• [17]Yahng SA, Kang HH, Kim SK, Lee SH, Moon HS, Lee BY, Kim HS, Seo EJ: Erdheim-Chester disease with lung involvement mimicking pulmonary lymphangitic carcinomatosis. Am J Med Sci 2009, 337:302-304.
• [18]Protopapadakis C, Antoniou KM, Nicholson AG, Voloudaki A, Tzanakis N, Karantanas A, Siafakas NM: Erdheim-Chester disease: pulmonary presentation in a case with advanced systemic involvement. Respiration 2009, 77:337-340.
• [19]Yelfimov DA, Lightner DJ, Tollefson MK: Urologic manifestations of Erdheim-Chester disease. Urology 2014, 84:218-221.
• [20]Wimpissinger TF, Schernthaner G, Feichtinger H, Stackl W: Compression of kidneys in Erdheim-Chester disease of retroperitoneum: open surgical approach. Urology 2005, 65:798.
• [21]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, 42:1107-1112.
• [22]Lee HJ, Lee KY, Shin DY, Lee YG, Choi SY, Moon KC, Han IK, Kim TM: A case of erdheim-chester disease with asymptomatic renal involvement. Cancer Res Treat 2012, 44:146-150.
• [23]Heller MT, Haarer KA, Thomas E, Thaete FL: Neoplastic and proliferative disorders of the perinephric space. Clin Radiol 2012, 67:e31-e41.
• [24]Haroche J, Amoura Z, Touraine P, Seilhean D, Graef C, Birmele B, Wechsler B, Cluzel P, Grenier PA, Piette JC: Bilateral adrenal infiltration in Erdheim-Chester disease. Report of seven cases and literature review. J Clin Endocrinol Metab 2007, 92:2007-2012.
• [25]Skinner M, Briant M, Morgan MB: Erdheim-Chester disease: a histiocytic disorder more than skin deep. Am J Dermatopathol 2011, 33:e24-e26.
• [26]Volpicelli ER, Doyle L, Annes JP, Murray MF, Jacobsen E, Murphy GF, Saavedra AP: Erdheim-Chester disease presenting with cutaneous involvement: a case report and literature review. J Cutan Pathol 2011, 38:280-285.
• [27]Opie KM, Kaye J, Vinciullo C: Erdheim-Chester disease. Australas J Dermatol 2003, 44:194-198.
• [28]Detlefsen S, Fagerberg CR, Ousager LB, Lindebjerg J, Marcussen N, Nathan T, Sørensen FB: Histiocytic disorders of the gastrointestinal tract. Hum Pathol 2013, 44:683-696.
• [29]Ivan D, Neto A, Lemos L, Gupta A: Erdheim-Chester disease: a unique presentation with liver involvement and vertebral osteolytic lesions. Arch Pathol Lab Med 2003, 127:e337-e339.
• [30]Gundling F, Nerlich A, Heitland WU, Schepp W: Biliary manifestation of Erdheim-Chester disease mimicking Klatskin’s carcinoma. Am J Gastroenterol 2007, 102:452-454.
• [31]Pan A, Doyle T, Schlup M, Lubcke R, Schultz M: Unusual manifestation of Erdheim-Chester disease. BMC Gastroenterol 2011, 11:77. BioMed Central Full Text
• [32]Tan AP, Tan LK, Choo IH: Erdheim-Chester disease involving breast and muscle: imaging findings. AJR Am J Roentgenol 1995, 164:1115-1117.
• [33]Barnes PJ, Foyle A, Hache KA, Langley RG, Burrell S, Juskevicius R: Erdheim-Chester disease of the breast: a case report and review of the literature. Breast J 2005, 11:462-467.
• [34]Provenzano E, Barter SJ, Wright PA, Forouhi P, Allibone R, Ellis IO: Erdheim-chester disease presenting as bilateral clinically malignant breast masses. Am J Surg Pathol 2010, 34:584-588.
• [35]Ambrosini V, Savelli F, Merli E, Zompatori M, Nanni C, Allegri V, Fanti S: F-18 FDG PET/CT detects muscle involvement in Erdheim-Chester disease. Clin Nucl Med 2012, 37:196-197.
• [36]Sheu SY, 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, 57:1225-1228.
• [37]Rao RN, Chang CC, Uysal N, Presberg K, Shidham VB, Tomashefski JF Jr: Fulminant multisystem non-langerhans cell histiocytic proliferation with hemophagocytosis: a variant form of Erdheim-Chester disease. Arch Pathol Lab Med 2005, 129:e39-e43.
• [38]Arnaud L, Hervier B, Neel A, Hamidou MA, Kahn JE, Wechsler B, Pérez-Pastor G, Blomberg B, Fuzibet JG, Dubourguet F, Marinho A, Magnette C, Noel V, Pavic M, Casper J, Beucher AB, Costedoat-Chalumeau N, Aaron L, Salvatierra J, Graux C, Cacoub P, Delcey V, Dechant C, Bindi P, Herbaut C, Graziani G, Amoura Z, Haroche J: CNS involvement and treatment with interferon-alpha are independent prognostic factors in Erdheim-Chester disease: a multicenter survival analysis of 53 patients. Blood 2011, 117:2778-2782.
• [39]Haroche J, Amoura Z, Dion E, Wechsler B, Costedoat-Chalumeau N, Cacoub P, Isnard R, Généreau T, Wechsler J, Weber N, Graef C, Cluzel P, Grenier P, Piette JC: Cardiovascular involvement, an overlooked feature of Erdheim-Chester disease: report of 6 new cases and a literature review. Medicine (Baltimore) 2004, 83:371-392.
• [40]Tran TA, Pariente D, Lecron JC, Delwail A, Taoufik Y, Meinzer U: Treatment of pediatric Erdheim-Chester disease with interleukin-1-targeting drugs. Arthritis Rheum 2011, 63:4031-4032.
• [41]Tran TA, Fabre M, Pariente D, Craiu I, Haroche J, Charlotte F, Eid P, Durrbach A, Taoufik Y, Kone-Paut I: Erdheim-Chester disease in childhood: a challenging diagnosis and treatment. J Pediatr Hematol Oncol 2009, 31:782-786.
• [42]Kumandas S, Kurtsoy A, Canoz O, Patiroglu T, Yikilmaz A, Per H: Erdheim Chester disease: cerebral involvement in childhood. Brain Dev 2007, 29:227-230.
• [43]Joo CU, Go YS, Kim IH, Kim CS, Lee SY: Erdheim-Chester disease in a child with MR imaging showing regression of marrow changes. Skeletal Radiol 2005, 34:299-302.
• [44]Clerico A, Ragni G, Cappelli C, Schiavetti A, Gonfiantini M, Uccini S: Erdheim-Chester disease in a child. Med Pediatr Oncol 2003, 41:575-577.
• [45]Tsai JW, Tsou JH, Hung LY, Wu HB, Chang KC: 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, 63:284-291.
• [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, 15:666-672.
• [47]Chetritt J, Paradis V, Dargere D, Adle-Biassette H, Maurage CA, Mussini JM, Vital A, Wechsler J, Bedossa P: Chester-Erdheim disease: a neoplastic disorder. Hum Pathol 1999, 30:1093-1096.
• [48]Vencio EF, Jenkins RB, Schiller JL, Huynh TV, Wenger DD, Inwards CY, Oliveira AM: Clonal cytogenetic abnormalities in Erdheim-Chester disease. Am J Surg Pathol 2007, 31:319-321.
• [49]Arnaud L, Gorochov G, Charlotte F, Lvovschi V, Parizot C, Larsen M, Ghillani-Dalbin P, Hervier B, Kahn JE, Deback C, Musset L, Amoura Z, Haroche J: Systemic perturbation of cytokine and chemokine networks in Erdheim-Chester disease: a single-center series of 37 patients. Blood 2011, 117:2783-2790.
• [50]Haroche J, Charlotte F, Arnaud L, von Deimling A, Helias-Rodzewicz Z, Hervier B, Cohen-Aubart F, Launay D, Lesot A, Mokhtari K, Canioni D, Galmiche L, Rose C, Schmalzing M, Croockewit S, Kambouchner M, Copin MC, Fraitag S, Sahm F, Brousse N, Amoura Z, Donadieu J, Emile JF: High prevalence of BRAF V600E mutations in Erdheim-Chester disease but not in other non-Langerhans cell histiocytoses. Blood 2012, 120:2700-2703.
• [51]Berres ML, Allen CE, Merad M: Pathological consequence of misguided dendritic cell differentiation in histiocytic diseases. Adv Immunol 2013, 120:127-161.
• [52]Mazor RD, Manevich-Mazor M, Shoenfeld Y: Strategies and treatment alternatives in the management of Erdheim–Chester disease. Expert Opinion Orphan Drugs 2013, 1:891-899.
• [53]Diamond EL, Dagna L, Hyman DM, Cavalli G, Janku F, Estrada-Veras J, Ferrarini M, Abdel-Wahab O, Heaney ML, Scheel PJ, Feeley NK, Ferrero E, McClain KL, Vaglio A, Colby T, Arnaud L, Haroche J: Consensus guidelines for the diagnosis and clinical management of Erdheim-Chester disease. Blood 2014, 124:483-492.
• [54]Braiteh F, Boxrud C, Esmaeli B, Kurzrock R: Successful treatment of Erdheim-Chester disease, a non-Langerhans-cell histiocytosis, with interferon-alpha. Blood 2005, 106:2992-2994.
• [55]Haroche J, Amoura Z, Trad SG, Wechsler B, Cluzel P, Grenier PA, Piette JC: Variability in the efficacy of interferon-alpha in Erdheim-Chester disease by patient and site of involvement: results in eight patients. Arthritis Rheum 2006, 54:3330-3336.
• [56]Hervier B, Arnaud L, Charlotte F, Wechsler B, Piette JC, Amoura Z, Haroche J: Treatment of Erdheim-Chester disease with long-term high-dose interferon-alpha. Semin Arthritis Rheum 2012, 41:907-913.
• [57]Aouba A, Georgin-Lavialle S, Pagnoux C, Martin Silva N, Renand A, Galateau-Salle F, Le Toquin S, Bensadoun H, Larousserie F, Silvera S, Provost N, Candon S, Seror R, de Menthon M, Hermine O, Guillevin L, Bienvenu B: Rationale and efficacy of interleukin-1 targeting in Erdheim-Chester disease. Blood 2010, 116:4070-4076.
• [58]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, 80:206-207.
• [59]Adam Z, Szturz P, Buckova P, Cervinkova I, Koukalova R, Rehak Z, Krejčí M, Pour L, Zahradová L, Hájek R, Král Z, Mayer J: Interleukin-1 receptor blockade with anakinra provided cessation of fatigue, reduction in inflammation markers and regression of retroperitoneal fibrosis in a patient with Erdheim-Chester disease - case study and a review of literature. Vnitr Lek 2012, 58:313-318. In Czech
• [60]Dagna L, Corti A, Langheim S, Guglielmi B, De Cobelli F, Doglioni C, Fragasso G, Sabbadini MG, Ferrarini M: Tumor necrosis factor alpha as a master regulator of inflammation in Erdheim-Chester disease: rationale for the treatment of patients with infliximab. J Clin Oncol 2012, 30:e286-e290.
• [61]Haroche J, Cohen-Aubart F, Emile JF, Arnaud L, Maksud P, Charlotte F, Cluzel P, Drier A, Hervier B, Benameur N, Besnard S, Donadieu J, Amoura Z: Dramatic efficacy of vemurafenib in both multisystemic and refractory Erdheim-Chester disease and Langerhans cell histiocytosis harboring the BRAF V600E mutation. Blood 2013, 121:1495-1500.
• [62]Blombery P, Wong SQ, Lade S, Prince HM: Erdheim-Chester disease harboring the BRAF V600E mutation. J Clin Oncol 2012, 30:e331-e332.
• [63]Adam Z, Szturz P, Pour L, Krejci M, Zahradova L, Tomiska M, Král Z, Koukalová R, Rehák Z, Mayer J: Cladribine is highly effective in the treatment of Langerhans cell histiocytosis and rare histiocytic disorders of the juvenile xanthogranuloma group. Vnitr Lek 2012, 58:455-465. In Czech
• [64]Adam Z, Sprlakova A, Rehak Z, Koukalova R, Szturz P, Krejci M, Pour L, Zahradová L, Cervinek L, Kren L, Moulis M, Hermanová M, Mechl M, Prásek J, Hájek R, Král Z, Mayer J: Partial regression of CNS lesions of Erdheim-Chester disease after treatment with 2-chlorodeoxadenosine and their full remission following treatment with lenalidomide. Klin Onkol 2011, 24:367-381. In Czech
• [65]Adam Z, Koukalova R, Sprlakova A, Rehak Z, Cervinek L, Szturz P, Krejcí M, Pour L, Zahradová L, Moulis M, Prásek J, Chaloupka R, Hájek R, Mayer J: Successful treatment of Erdheim-Chester disease by 2-chlorodeoxyadenosine-based chemotherapy. Two case studies and a literature review. Vnitr Lek 2011, 57:576-589. In Czech
• [66]Myra C, Sloper L, Tighe PJ, McIntosh RS, Stevens SE, Gregson RH, Sokal M, Haynes AP, Powell RJ: Treatment of Erdheim-Chester disease with cladribine: a rational approach. Br J Ophthalmol 2004, 88:844-847.
• [67]Smith JR, Rosenbaum JT: A role for methotrexate in the management of non-infectious orbital inflammatory disease. Br J Ophthalmol 2001, 85:1220-1224.
• [68]Jendro MC, Zeidler H, Rosenthal H, Haller H, Schwarz A: Improvement of Erdheim-Chester disease in two patients by sequential treatment with vinblastine and mycophenolate mofetil. Clin Rheumatol 2004, 23:52-56.
• [69]Broccoli A, Stefoni V, Faccioli L, Agostinelli C, Spinardi L, Pastore Trossello M, Zinzani PL: Bilateral orbital Erdheim-Chester disease treated with 12 weekly administrations of VNCOP-B chemotherapy: a case report and a review of literature. Rheumatol Int 2012, 32:2209-2213.
• [70]Badzek S, Misir-Krpan A, Krajina Z, Radman I, Stern-Padovan R, Dotlic S: Erdheim-Chester disease and concomitant tuberculosis successfully treated with chemotherapy and long-term steroids. Coll Antropol 2007, 31:621-623.
• [71]Franco P, Filippi AR, Ciammella P, Botticella A, Namysl-Kaletka A, Ricardi U: Polyostotic sclerosing histiocytosis (Erdheim-Chester disease) treated with combined vertebroplasty and radiation therapy. Tumori 2010, 96:633-636.
• [72]Matsui K, Nagata Y, Hiraoka M: Radiotherapy for Erdheim-Chester disease. Int J Clin Oncol 2007, 12:238-241.
• [73]Miller RC, Villa S, Kamer S, Pasquier D, Poortmans P, Micke O, Call TG: Palliative treatment of Erdheim-Chester disease with radiotherapy: a Rare Cancer Network study. Radiother Oncol 2006, 80:323-326.
• [74]Mascalchi M, Nencini P, Nistri M, Sarti C, Santoni R: Failure of radiation therapy for brain involvement in Erdheim Chester disease. J Neurooncol 2002, 59:169-172.
• [75]Veyssier-Belot C, Cacoub P, Caparros-Lefebvre D, Wechsler J, Brun B, Remy M, Wallaert B, Petit H, Grimaldi A, Wechsler B, Godeau P: Erdheim-Chester disease. Clinical and radiologic characteristics of 59 cases. Medicine (Baltimore) 1996, 75:157-169.
• [76]Mossetti G, Rendina D, Numis FG, Somma P, Postiglione L, Nunziata V: Biochemical markers of bone turnover, serum levels of interleukin-6/interleukin-6 soluble receptor and bisphosphonate treatment in Erdheim-Chester disease. Clin Exp Rheumatol 2003, 21:232-236.
• [77]Eyigor S, Kirazli Y, Memis A, Basdemir G: Erdheim-Chester disease: the effect of bisphosphonate treatment–a case report. Arch Phys Med Rehabil 2005, 86:1053-1057.
• [78]Srikulmontree T, Massey HD, Roberts WN: Treatment of skeletal Erdheim-Chester disease with zoledronic acid: case report and proposed mechanisms of action. Rheumatol Int 2007, 27:303-307.
• [79]Boissel N, Wechsler B, Leblond V: Treatment of refractory Erdheim-Chester disease with double autologous hematopoietic stem-cell transplantation. Ann Intern Med 2001, 135:844-845.
• [80]Gaspar N, Boudou P, Haroche J, Wechsler B, Van Den Neste E, Hoang-Xuan K, Amoura Z, Guillevin R, Savatovski J, Azar N, Piette JC, Leblond V: High-dose chemotherapy followed by autologous hematopoietic stem cell transplantation for adult histiocytic disorders with central nervous system involvement. Haematologica 2006, 91:1121-1125.
• [81]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. Ann Rheum Dis 2013, 72:1691-1695.
• [82]O'Rourke R, Wong DC, Fleming S, Walker D: Erdheim-Chester disease: a rare cause of acute renal failure. Australas Radiol 2007, 51:Spec No.:B48-B51.
• [83]Jeon IS, Lee SS, Lee MK: Chemotherapy and interferon-alpha treatment of Erdheim-Chester disease. Pediatr Blood Cancer 2010, 55:745-747.
• [84]Diamond EL, Abdel-Wahab O, Pentsova E, Borsu L, Chiu A, Teruya-Feldstein J, Hyman DM, Rosenblum M: Detection of an NRAS mutation in Erdheim-Chester disease. Blood 2013, 122:1089-1091.
• [85]Cangi MG, Biavasco R, Cavalli G, Grassini G, Dal-Cin E, Campochiaro C, Guglielmi B, Berti A, Lampasona V, von Deimling A, Sabbadini MG, Ferrarini M, Doglioni C, Dagna L: BRAFV600E-mutation is invariably present and associated to oncogene-induced senescence in Erdheim-Chester disease. Ann Rheum Dis 2014.