Vol 52, No 6 (2021)
Original research article
Published online: 2021-11-08

open access

Page views 5941
Article views/downloads 351
Get Citation

Connect on Social Media

Connect on Social Media

From classical Langerhans cell histiocytosis to Erdheim-Chester disease: different sides of the same coin?

Elżbieta Grześk1, Anna Dąbrowska1, Sylwia Kołtan1, Mariusz Wysocki1, Krzysztof Czyżewski1, Jan Styczyński1
Acta Haematol Pol 2021;52(6):571-577.


Objective. Analysis of the clinical course of classical histiocytosis (LCH) in children and clinical differences, diagnostic difficulties and a different therapeutic strategy in a child with a rare variant of LCH in the form of Erdheim-Chester syndrome (ECD). Patients and methods. Retrospective single-center analysis of the clinical course of classic LCH in 54 children who were diagnosed with the disease in the last 40 years and the differences shown in a patient with diagnosed EDC. The clinical response was assessed according to the LCH programs valid at the time for the classic form of LCH and in the child with ECD. Results. The multi-system form of LCH was diagnosed more often than the single-system form. The skull bones were the most common localization of LCH in both forms of the disease. Recurrence of the disease occurred in about 5% of patients, death in one (1.9%) patient. The course of the child with ECD was more turbulent, with rapid progression, involvement of critical organs, no response to standard chemotherapy according to the LCH 2009 protocol. After the molecular diagnosis was specified, therapy with vemurafenib, a BRAF-V600E kinase inhibitor, followed by transplantation of hematopoietic stem cells (allo-HCT) was applied. Basic disease was in remission and lasts for 12 months. Conclusions. The lack of an expected response to LCH therapy should indicate the possibility of rare forms of histiocytic hyperplasia. Molecular tests are an important element in the diagnosis of histiocytosis and allow to precisely select the most appropriate, targeted therapy. BRAF-V600E kinase inhibitors are highly safe and effective in the treatment of LCH and ECD with a confirmed BRAF-V600E mutation, however allo-HCT should be considered in selected cases.

Article available in PDF format

View PDF Download PDF file


  1. Raciborska A, Małas Z, Tysarowski A. [Vemurafenib in refractory langerhans histiocytosis] [Article in Polish]. Dev Period Med. 2018; 22(4): 376–378.
  2. Drabko K, Raciborska A. Standard diagnostyki histiocytozy z komórek Langerhansa (Langerhans cell histiocytosis — LCH) w Polsce. Przegl Pediatr. 2019; 48(3): 72–74.
  3. Goyal G, Heaney ML, Collin M, et al. Erdheim-Chester disease: consensus recommendations for evaluation, diagnosis, and treatment in the molecular era. Blood. 2020; 135(22): 1929–1945.
  4. Haroche J, Cohen-Aubart F, Amoura Z. Erdheim-Chester disease. Blood. 2020; 135(16): 1311–1318.
  5. Arnaud L, Hervier B, Néel A, 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; 117(10): 2778–2782.
  6. Hervier B, Haroche J, Arnaud L, et al. French Histiocytoses Study Group. Association of both Langerhans cell histiocytosis and Erdheim-Chester disease linked to the BRAFV600E mutation. Blood. 2014; 124(7): 1119–1126.
  7. Nagatsuka H, Han PP, Taguchi K, et al. Erdheim-Chester disease in a child presenting with multiple jaw lesions. J Oral Pathol Med. 2005; 34(7): 420–422.
  8. Haroche J, Cohen-Aubart F, Rollins BJ, et al. Histiocytoses: emerging neoplasia behind inflammation. Lancet Oncol. 2017; 18(2): e113–e125.
  9. Rodriguez-Galindo C, Allen C. Langerhans cell histiocytosis. Blood. 2020; 135(16): 1319–1331.
  10. Radzikowska E. Pulmonary Langerhans' cell histiocytosis in adults. Adv Respir Med. 2017; 85(5): 277–289.
  11. Diamond EL, Dagna L, Hyman DM, et al. Consensus guidelines for the diagnosis and clinical management of Erdheim-Chester disease. Blood. 2014; 124(4): 483–492.
  12. Khan MR, Ashraf M, Belgaumi A. Erdheim Chester disease — an unusual presentation of a rare histiocytic disease in a 3-year old boy. Pediatric Hematology Oncology Journal. 2017; 2(3): 59–62.
  13. Haroche J, Arnaud L, Cohen-Aubart F, et al. Erdheim-Chester disease. Curr Rheumatol Rep. 2014; 16(4): 412.
  14. McClain K. Histiocytic disorders: insights into novel biology and implications for therapy of Langerhans cell histiocytosis and Erdheim-Chester disease. Hematology Am Soc Hematol Educ Program. 2020; 2020(1): 395–399.
  15. Starkebaum G, Hendrie P. Erdheim-Chester disease. Best Pract Res Clin Rheumatol. 2020; 34(4): 101510.
  16. Haroche J, Abla O. Uncommon histiocytic disorders: Rosai-Dorfman, juvenile xanthogranuloma, and Erdheim-Chester disease. Hematology Am Soc Hematol Educ Program. 2015; 2015: 571–578.
  17. Picarsic J, Pysher T, Zhou H, et al. BRAF V600E mutation in juvenile xanthogranuloma family neoplasms of the central nervous system (CNS-JXG): a revised diagnostic algorithm to include pediatric Erdheim-Chester disease. Acta Neuropathol Commun. 2019; 7(1): 168.
  18. Cohen Aubart F, Roos-Weil D, Armand M, et al. High frequency of clonal hematopoiesis in Erdheim-Chester disease. Blood. 2021; 137(4): 485–492.
  19. Cohen-Aubart F, Emile JF, Carrat F, et al. Phenotypes and survival in Erdheim-Chester disease: results from a 165-patient cohort. Am J Hematol. 2018; 93(5): E114–E117.
  20. Lachenal F, Cotton F, Desmurs-Clavel H, et al. Neurological manifestations and neuroradiological presentation of Erdheim-Chester disease: report of 6 cases and systematic review of the literature. J Neurol. 2006; 253(10): 1267–1277.
  21. Arnaud L, Pierre I, Beigelman-Aubry C, 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; 62(11): 3504–3512.
  22. Goyal G, Young JR, Koster MJ, et al. Mayo Clinic Histiocytosis Working Group. The Mayo Clinic Histiocytosis Working Group Consensus Statement for the Diagnosis and Evaluation of Adult Patients With Histiocytic Neoplasms: Erdheim-Chester Disease, Langerhans Cell Histiocytosis, and Rosai-Dorfman Disease. Mayo Clin Proc. 2019; 94(10): 2054–2071.
  23. Song SY, Lee SW, Ryu KH, et al. Erdheim-Chester disease with multisystem involvement in a 4-year-old. Pediatr Radiol. 2012; 42(5): 632–635.
  24. Tran TA, Fabre M, Pariente D, et al. Erdheim-Chester disease in childhood: a challenging diagnosis and treatment. J Pediatr Hematol Oncol. 2009; 31(10): 782–786.
  25. Cives M, Simone V, Rizzo FM, et al. Erdheim-Chester disease: a systematic review. Crit Rev Oncol Hematol. 2015; 95(1): 1–11.
  26. Papo M, Emile JF, Maciel TT, et al. Erdheim-Chester disease: a concise review. Curr Rheumatol Rep. 2019; 21(12): 66.
  27. Campochiaro C, Cavalli G, Farina N, et al. Efficacy and improved tolerability of combination therapy with interleukin-1 blockade and MAPK pathway inhibitors for the treatment of Erdheim-Chester disease. Ann Rheum Dis. 2019 [Epub ahead of print].
  28. Papo M, Diamond EL, Cohen-Aubart F, et al. High prevalence of myeloid neoplasms in adults with non-Langerhans cell histiocytosis. Blood. 2017; 130(8): 1007–1013.
  29. Haupt R, Minkov M, Astigarraga I, et al. Euro Histio Network. Langerhans cell histiocytosis (LCH): guidelines for diagnosis, clinical work-up, and treatment for patients till the age of 18 years. Pediatr Blood Cancer. 2013; 60(2): 175–184.
  30. Váradi Z, Bánusz R, Csomor J, et al. Effective BRAF inhibitor vemurafenib therapy in a 2-year-old patient with sequentially diagnosed Langerhans cell histiocytosis and Erdheim-Chester disease. Onco Targets Ther. 2017; 10: 521–526.