Immunity Disorders
Questions Received:
Response:
My brother died of a very rare blood disorder in 1960. He was approximately two years old. The disease is Leteraseewe. I am trying to find information about it.
7th March 2000
In Letterer-Siwe disease there is an over-production of specialised cells that form part of the body’s defence system. The disease generally occurs in very young children and is often fatal. The cells concerned are called Langerhans cells, and their normal role is to detect non-self antigens (molecular markers that are not normal constituents of the body) and then present them to the cells of the immune system so that an appropriate immune response can be organised. Langerhans cells are normally found in the epidermis of the skin, but in Letterer-Siwe disease they spread to bone and other tissues of the body.
Some of the terminology that relates to this condition is obscure and is in the process of being changed. This will complicate your search for information. However, the following points may be helpful:
There is a family of related conditions that used to be called histiocytosis X (first named by Lichtenstein in 1953), and Letterer-Siwe disease forms part of this spectrum. The three main members of histiocytosis X are Letterer-Siwe disease, Hand-Schüller-Christian disease, and eosinophilic granuloma. All of these are characterised by a distinctive inflammatory and proliferative process, but they differ from each other in which parts of the body are involved and the course of the disease.
Recent research has confirmed the involvement of Langerhans cells, and this has led to the proposal that the term Langerhans cell histiocytosis should be used in place of histiocytosis X (eg: Hefti and Jundt, 1995).
There has also been a call to refer to all these related conditions as Langerhans cell granulomatosis (Lieberman et al, 1996). This is based on the grounds that the Langerhans’ cell is not a tissue macrophage in the usual sense and therefore should not be classified as a histiocyte.
It appears that the proliferation of Langerhans' cells in Letterer-Siwe disease is due to disturbances in the way that the immune system is regulated (Hefti and Jundt, 1995; Bianchi and Cataldi, 1999). Abnormal colonies of dividing Langerhans cells occur primarily in bone, but lung, skin, and lymph node involvement is not uncommon while involvement of thyroid, thymus, and other sites is rare (Lieberman et al, 1996). The infiltrating Langerhans cells can be recognised under the electron microscope by their intracytoplasmic Birbeck granules (Veyssier-Belot and Callot, 1996). Langerhans cells normally communicate with T cells in the immune system, but in some forms of Langerhans cell histiocytosis they become associated with another type of white blood cell - the eosinophil.
Helpful overviews of Letterer-Siwe disease can be found in Gianotti and Caputo (1985) and Velez-Yanguas and Warrier (1996). An historical overview of Langerhans cell histiocytosis is provided by Komp (1987), and a review of the radiographic appearances is given by Stull, Kransdorf, and Devaney (1992).
References
Bianchi, M., and Cataldi, M. (1999) Pneumothorax secondary to pulmonary histiocytosis X. [Article in Italian] Minerva Chir, 54(7-8), 531-536 (Jul-Aug).
Gianotti, F., and Caputo, R. (1985) Histiocytic syndromes: a review. Journal of the American Academy of Dermatology, 13(3), 383-404 (Sep).
Hefti, F., and Jundt, G. (1995) Langerhans cell histiocytosis. [Article in German] Orthopade, 24(1), 73-81 (Feb).
Komp, D.M. (1987) Historical perspectives of Langerhans cell histiocytosis. Hematology and Oncology Clinics North America, 1(1), 9-21 (Mar).
Lieberman, P.H., Jones, C.R., Steinman, R.M., Erlandson, R.A., Smith, J., Gee, T., Huvos, A., Garin-Chesa, P., Filippa, D.A., Urmacher, C., Gangi, M.D., and Sperber, M. (1996) Langerhans cell (eosinophilic) granulomatosis. A clinicopathologic study encompassing 50 years. American Journal of Surgical Pathology, 20(5), 519-552 (May).
Stull, M.A., Kransdorf, M.J., and Devaney, K.O. (1992) Langerhans cell histiocytosis of bone. Radiographics, 12(4), 801-823 (Jul).
Velez-Yanguas, M.C., and Warrier, R.P. (1996) Langerhans' cell histiocytosis. Orthopedic Clinics North America, 27(3), 615-623 (Jul).
Veyssier-Belot, C., and Callot, V. (1996) Histiocytosis. [Article in French] Rev Med Interne, 17(11), 911-923.