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. 1994 Sep;23:S11–S16.

Langerhans cell histiocytosis--clinical and epidemiological aspects.

V Broadbent 1, R M Egeler 1, M E Nesbit Jr 1
PMCID: PMC2149699  PMID: 8075001

Abstract

Langerhans cell histiocytosis is a disease which frustrates both clinician and scientist. Its aetiology is unknown, its pathogenesis is ill understood and the clinical course is unpredictable. Historically, the different nomenclatures reflecting the first clinical descriptions by Hand (1893, 1921), Schuller (1915) and Christian (1920), and subsequently by Letterer (1924) and Siwe (1933), led to confusion only partially resolved by Lichtenstein (1953) who recognised that the disease in each of these clinical syndromes were components of a spectrum of disease involving the histiocyte. He proposed his unifying concept of Histiocytosis X--'X' being the unknown aetiological factor. In 1973, Nezelof recognised the lesional cell as a 'Langerhans-like' cell but it took another decade for the disease to be recognised as a single entity and the term Langerhans cell histiocytosis to be internationally accepted. The publication, by the Histiocyte Society (1987), of their classification of the histiocyte disorders together with criteria for pathological diagnosis and clinical evaluation of Langerhans cell histiocytosis have consolidated the position. This article details the wide variety of clinical manifestations of the disease and its sequelae and discusses possible epidemiological factors. Finally it looks at the potential implications of recent scientific research on the management of the disease.

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Selected References

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  1. Arenzana-Seisdedos F., Barbey S., Virelizier J. L., Kornprobst M., Nezelof C. Histiocytosis X. Purified (T6+) cells from bone granuloma produce interleukin 1 and prostaglandin E2 in culture. J Clin Invest. 1986 Jan;77(1):326–329. doi: 10.1172/JCI112296. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Barbey S., Gane P., Le Pelletier O., Nezelof C. Histiocytosis X Langerhans cells react with antiinterleukin-2 receptor monoclonal antibody. Pediatr Pathol. 1987;7(5-6):569–574. doi: 10.3109/15513818709161420. [DOI] [PubMed] [Google Scholar]
  3. Brandt L. J., Broadbent V. Nephrotoxicity following carboplatin use in children: is routine monitoring of renal function necessary? Med Pediatr Oncol. 1993;21(1):31–35. doi: 10.1002/mpo.2950210107. [DOI] [PubMed] [Google Scholar]
  4. Braunstein G. D., Kohler P. O. Endocrine manifestations of histiocytosis. Am J Pediatr Hematol Oncol. 1981 Spring;3(1):67–75. [PubMed] [Google Scholar]
  5. Broadbent V., Gadner H., Komp D. M., Ladisch S. Histiocytosis syndromes in children: II. Approach to the clinical and laboratory evaluation of children with Langerhans cell histiocytosis. Clinical Writing Group of the Histiocyte Society. Med Pediatr Oncol. 1989;17(6):492–495. doi: 10.1002/mpo.2950170527. [DOI] [PubMed] [Google Scholar]
  6. Broadbent V., Pritchard J. Histiocytosis X--current controversies. Arch Dis Child. 1985 Jul;60(7):605–607. doi: 10.1136/adc.60.7.605. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Caux C., Dezutter-Dambuyant C., Schmitt D., Banchereau J. GM-CSF and TNF-alpha cooperate in the generation of dendritic Langerhans cells. Nature. 1992 Nov 19;360(6401):258–261. doi: 10.1038/360258a0. [DOI] [PubMed] [Google Scholar]
  8. Ceci A., de Terlizzi M., Colella R., Loiacono G., Balducci D., Surico G., Castello M., Testi A. M., De Bernardi B., Indolfi P. Langerhans cell histiocytosis in childhood: results from the Italian Cooperative AIEOP-CNR-H.X '83 study. Med Pediatr Oncol. 1993;21(4):259–264. doi: 10.1002/mpo.2950210405. [DOI] [PubMed] [Google Scholar]
  9. Crone-Münzebrock W., Brassow F. A comparison of radiographic and bone scan findings in histiocytosis X. Skeletal Radiol. 1983;9(3):170–173. doi: 10.1007/BF00352548. [DOI] [PubMed] [Google Scholar]
  10. Davies E. G., Levinsky R. J., Butler M., Broadbent V., Pritchard J., Chessells J. Thymic hormone therapy for histiocytosis X? N Engl J Med. 1983 Aug 25;309(8):493–494. [PubMed] [Google Scholar]
  11. Dean H. J., Bishop A., Winter J. S. Growth hormone deficiency in patients with histiocytosis X. J Pediatr. 1986 Oct;109(4):615–618. doi: 10.1016/s0022-3476(86)80223-2. [DOI] [PubMed] [Google Scholar]
  12. Dunger D. B., Broadbent V., Yeoman E., Seckl J. R., Lightman S. L., Grant D. B., Pritchard J. The frequency and natural history of diabetes insipidus in children with Langerhans-cell histiocytosis. N Engl J Med. 1989 Oct 26;321(17):1157–1162. doi: 10.1056/NEJM198910263211704. [DOI] [PubMed] [Google Scholar]
  13. Egeler R. M., Neglia J. P., Puccetti D. M., Brennan C. A., Nesbit M. E. Association of Langerhans cell histiocytosis with malignant neoplasms. Cancer. 1993 Feb 1;71(3):865–873. doi: 10.1002/1097-0142(19930201)71:3<865::aid-cncr2820710334>3.0.co;2-0. [DOI] [PubMed] [Google Scholar]
  14. Egeler R. M., Thompson R. C., Jr, Voûte P. A., Nesbit M. E., Jr Intralesional infiltration of corticosteroids in localized Langerhans' cell histiocytosis. J Pediatr Orthop. 1992 Nov-Dec;12(6):811–814. doi: 10.1097/01241398-199211000-00021. [DOI] [PubMed] [Google Scholar]
  15. Favara B. E. Langerhans' cell histiocytosis pathobiology and pathogenesis. Semin Oncol. 1991 Feb;18(1):3–7. [PubMed] [Google Scholar]
  16. Friedman P. J., Liebow A. A., Sokoloff J. Eosinophilic granuloma of lung. Clinical aspects of primary histiocytosis in the adult. Medicine (Baltimore) 1981 Nov;60(6):385–396. [PubMed] [Google Scholar]
  17. Fromer J. L., Jaffe N. Urticaria pigmentosa and acute lymphoblastic leukemia. Arch Dermatol. 1973 Feb;107(2):283–284. [PubMed] [Google Scholar]
  18. Gadner H., Heitger A., Ritter J., Göbel U., Janka G. E., Kühl J., Bode U., Spaar H. J. Langerhanszell-Histiozytose im Kindesalter--Ergebnisse der DAL-HX 83 Studie. Klin Padiatr. 1987 May-Jun;199(3):173–182. doi: 10.1055/s-2008-1026785. [DOI] [PubMed] [Google Scholar]
  19. Greenberger J. S., Crocker A. C., Vawter G., Jaffe N., Cassady J. R. Results of treatment of 127 patients with systemic histiocytosis. Medicine (Baltimore) 1981 Sep;60(5):311–338. doi: 10.1097/00005792-198109000-00001. [DOI] [PubMed] [Google Scholar]
  20. Hosoi J., Murphy G. F., Egan C. L., Lerner E. A., Grabbe S., Asahina A., Granstein R. D. Regulation of Langerhans cell function by nerves containing calcitonin gene-related peptide. Nature. 1993 May 13;363(6425):159–163. doi: 10.1038/363159a0. [DOI] [PubMed] [Google Scholar]
  21. Irving R. M., Broadbent V., Jones N. S. Langerhans' cell histiocytosis in childhood: management of head and neck manifestations. Laryngoscope. 1994 Jan;104(1 Pt 1):64–70. doi: 10.1288/00005537-199401000-00011. [DOI] [PubMed] [Google Scholar]
  22. Keeling J. W., Harries J. T. Intestinal malabsorption in infants with histiocytosis X. Arch Dis Child. 1973 May;48(5):350–354. doi: 10.1136/adc.48.5.350. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Komp D. M., El Mahdi A., Starling K. A., Easley J., Vietti T. J., Berry D. H., George S. L. Quality of survival in histiocytosis X: a Southwest Oncology Group study. Med Pediatr Oncol. 1980;8(1):35–40. doi: 10.1002/mpo.2950080106. [DOI] [PubMed] [Google Scholar]
  24. Komp D. M. Langerhans cell histiocytosis. N Engl J Med. 1987 Mar 19;316(12):747–748. doi: 10.1056/NEJM198703193161211. [DOI] [PubMed] [Google Scholar]
  25. LICHTENSTEIN L. Histiocytosis X; integration of eosinophilic granuloma of bone, Letterer-Siwe disease, and Schüller-Christian disease as related manifestations of a single nosologic entity. AMA Arch Pathol. 1953 Jul;56(1):84–102. [PubMed] [Google Scholar]
  26. Lahey M. E., Rallison M. L., Hilding D. A., Ater J. Involvement of the thyroid in histiocytosis X. Am J Pediatr Hematol Oncol. 1986 Fall;8(3):257–259. [PubMed] [Google Scholar]
  27. Lichtenstein L., Jeffe H. L. Eosinophilic granuloma of bone: With report of a case. Am J Pathol. 1940 Sep;16(5):595–604.3. [PMC free article] [PubMed] [Google Scholar]
  28. Luger T. A. Epidermal cytokines. Acta Derm Venereol Suppl (Stockh) 1989;151:61–110. doi: 10.1007/978-3-642-83360-1_71. [DOI] [PubMed] [Google Scholar]
  29. Marcy T. W., Reynolds H. Y. Pulmonary histiocytosis X. Lung. 1985;163(3):129–150. doi: 10.1007/BF02713816. [DOI] [PubMed] [Google Scholar]
  30. McClain K., Ramsay N. K., Robison L., Sundberg R. D., Nesbit M., Jr Bone marrow involvement in histiocytosis X. Med Pediatr Oncol. 1983;11(3):167–171. doi: 10.1002/mpo.2950110307. [DOI] [PubMed] [Google Scholar]
  31. McLelland J., Broadbent V., Yeomans E., Malone M., Pritchard J. Langerhans cell histiocytosis: the case for conservative treatment. Arch Dis Child. 1990 Mar;65(3):301–303. doi: 10.1136/adc.65.3.301. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. McLelland J., Pritchard J., Chu A. C. Current controversies. Histiocytosis-X. Hematol Oncol Clin North Am. 1987 Mar;1(1):147–162. [PubMed] [Google Scholar]
  33. Mogul M., Hartman G., Donaldson S., Gelb A., Link M., Amylon M., Glader B. Langerhans' cell histiocytosis presenting with the superior vena cava syndrome: a case report. Med Pediatr Oncol. 1993;21(6):456–459. doi: 10.1002/mpo.2950210614. [DOI] [PubMed] [Google Scholar]
  34. Nesbit M. E., Jr, O'Leary M., Dehner L. P., Ramsay N. K. The immune system and the histiocytosis syndromes. Am J Pediatr Hematol Oncol. 1981 Summer;3(2):141–149. [PubMed] [Google Scholar]
  35. Nezelof C., Basset F., Rousseau M. F. Histiocytosis X histogenetic arguments for a Langerhans cell origin. Biomedicine. 1973 Sep;18(5):365–371. [PubMed] [Google Scholar]
  36. Osband M. E., Lipton J. M., Lavin P., Levey R., Vawter G., Greenberger J. S., McCaffrey R. P., Parkman R. Histiocytosis-X. N Engl J Med. 1981 Jan 15;304(3):146–153. doi: 10.1056/NEJM198101153040304. [DOI] [PubMed] [Google Scholar]
  37. Otani S., Ehrlich J. C. Solitary granuloma of bone: Simulating primary neoplasm. Am J Pathol. 1940 Jul;16(4):479–490.7. [PMC free article] [PubMed] [Google Scholar]
  38. Risdall R. J., Dehner L. P., Duray P., Kobrinsky N., Robison L., Nesbit M. E., Jr Histiocytosis X (Langerhans' cell histiocytosis). Prognostic role of histopathology. Arch Pathol Lab Med. 1983 Feb;107(2):59–63. [PubMed] [Google Scholar]
  39. Rosenfield N. S., Abrahams J., Komp D. Brain MR in patients with Langerhans cell histiocytosis: findings and enhancement with Gd-DTPA. Pediatr Radiol. 1990;20(6):433–436. doi: 10.1007/BF02075201. [DOI] [PubMed] [Google Scholar]
  40. Sacks S. H., Hall I., Ragge N., Pritchard J. Chronic dermal sinuses as a manifestation of histiocytosis X. Br Med J (Clin Res Ed) 1986 Apr 26;292(6528):1097–1098. doi: 10.1136/bmj.292.6528.1097. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Sheehan M. P., Atherton D. J., Broadbent V., Pritchard J. Topical nitrogen mustard: an effective treatment for cutaneous Langerhans cell histiocytosis. J Pediatr. 1991 Aug;119(2):317–321. doi: 10.1016/s0022-3476(05)80752-8. [DOI] [PubMed] [Google Scholar]
  42. Siegal G. P., Dehner L. P., Rosai J. Histiocytosis X (Langerhans' cell granulomatosis) of the thymus. A clinicopathologic study of four childhood cases. Am J Surg Pathol. 1985 Feb;9(2):117–124. doi: 10.1097/00000478-198502000-00006. [DOI] [PubMed] [Google Scholar]
  43. Silberberg I. Apposition of mononuclear cells to langerhans cells in contact allergic reactions. An ultrastructural study. Acta Derm Venereol. 1973;53(1):1–12. [PubMed] [Google Scholar]
  44. Sims D. G. Histiocytosis X; follow-up of 43 cases. Arch Dis Child. 1977 Jun;52(6):433–440. doi: 10.1136/adc.52.6.433. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Starling K. A. Chemotherapy of histiocytosis-X. Hematol Oncol Clin North Am. 1987 Mar;1(1):119–122. [PubMed] [Google Scholar]
  46. Stingl G., Tamaki K., Katz S. I. Origin and function of epidermal Langerhans cells. Immunol Rev. 1980;53:149–174. doi: 10.1111/j.1600-065x.1980.tb01043.x. [DOI] [PubMed] [Google Scholar]
  47. Streilein J. W. Skin-associated lymphoid tissues (SALT): origins and functions. J Invest Dermatol. 1983 Jun;80 (Suppl):12s–16s. doi: 10.1111/1523-1747.ep12536743. [DOI] [PubMed] [Google Scholar]
  48. Yu R. C., Attra A., Quinn C. M., Krausz T., Chu A. C. Multisystem Langerhans' cell histiocytosis with pancreatic involvement. Gut. 1993 Apr;34(4):570–572. doi: 10.1136/gut.34.4.570. [DOI] [PMC free article] [PubMed] [Google Scholar]

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