Letterer-Siwe Disease

Christie et al. (1954) described the disease in sibs who were never in contact, thus tending to discredit an infectious hypothesis. Rogers and Benson (1962) reported affected sibs and reviewed the literature. Falk and Gellei (1963) also observed a family. Schoeck et al. (1963) described 2 sibs with L-S disease. Ten other families with multiple affected sibs were reviewed, including Farquhar 'familial hemophagocytic reticulosis' (267700) and Nelson 'generalized lymphohistiocytic infiltration' (also see 267700), which Schoeck et al. suggested are all the same entity. In a survey of deaths from Letterer-Siwe disease in a 5-year period in the U.S., Glass and Miller (1968) found 5 sib pairs among 270 deaths, a pair of concordant like-sex twins, and a peak of mortality under 1 year of age. Freundlich et al. (1972) reported 2 families with multiple cases of consanguineous parents. Hirsch and Kong (1973) reported a father and son with histiocytosis X of the lung. The father presented with cough and exertional dyspnea, whereas the son was asymptomatic. Biopsies confirmed histiocytosis X (eosinophilic granuloma) in both. Neither father nor son had any evidence of disseminated histiocytosis. I have information from Cook (1967) concerning 8 cases of histiocytosis X occurring in 2 sibships in an inbred Mennonite group in Waterloo County, Ontario. In each case the parents were related as second cousins and all 4 parents shared in common a grandparental couple. In 2 cases, treatment with adrenocorticosteroids was begun early and both patients survived. The other cases pursued an identical course. They were well until ages 8 to 18 weeks, following which they developed general irritability, especially on being touched or moved. There was pallor, dyspnea, distended abdomen, fever, and, in the terminal stages, usually jaundice. Medical investigations showed hepatosplenomegaly, anemia, neutropenia, and thrombocytopenia. Autopsy showed histiocytic infiltration of the liver, spleen and lymph nodes. There was no persistent skin rash and no bone lesions were identified. The course of the illness in all 6 fatal cases was rapid, ranging from 2 to 5 weeks. None of the children had contact with each other. These cases are also discussed under familial histiocytic reticulosis (267700). The nosology of this category is confused, as is the terminology. For example, Donohue and Thompson (1972) concluded that the Mennonite cases represent the disorder reported as 'familial Letterer-Siwe disease' and not histiocytosis X. The occurrence of 'encephalopathy' in both the Mennonite cases and reported familial Letterer-Siwe disease, but not in either nonfamilial L-S disease or histiocytosis X, was one reason for their conclusion. Kloepfer et al. (1972) observed the same or a similar disorder in an inbred triracial group in Louisiana, known locally as 'Redbones.'

The entity described here should not be confused with Langerhans cell histiocytosis (604856) The Langerhans cell, a dendritic cell of the epidermis, was described by a medical student, Paul Langerhans, who thought that it was part of the nervous system (Langerhans, 1868). Birbeck et al. (1961) found that the Langerhans cell displays a unique electron-microscopic morphology. The discoveries that these cells are not confined to skin and that they make up a sizable portion of the cellular infiltrate in histiocytosis X, along with other evidence, suggest that they play an immunologic role in protecting against environmental antigens. Egeler and D'Angio (1995) presented a classification of histiocytosis syndromes in children: class I, Langerhans cell histiocytosis; class II, histiocytosis of mononuclear macrophages other than Langerhans cells, including familial hemophagocytic lymphohistiocytosis; and class III, malignant histiocytic disorders, including histiocytic lymphoma.