ABSTRACT
OBJECTIVE: The etiology and pathogenesis of Langerhans cell histiocytosis (LCH) remain poorly understood. We conducted an exploratory epidemiologic study to investigate potential risk factors associated with LCH. STUDY DESIGN: We used a case-control study design to obtain data from parents of children with LCH (n = 459) who were members of the Histiocytosis Association of America and Canada. The two control groups consisted of 683 community control subjects and 3719 children with childhood cancers treated at participating Children's Cancer Group institutions. RESULTS: The median age at diagnosis of LCH was 1.8 years (range 0.1 to 14.6 years). Cases were categorized as multisystem LCH (MS-LCH) (n = 208) and single-system LCH (SS-LCH) (n = 198). Statistically significant associations included the following: infections in the neonatal period (MS-LCH, odds ratio (OR) = 2.2), solvent exposure (SS-LCH, OR = 54.9), childhood vaccinations (MS-LCH and SS-LCH, OR = 0.4), thyroid disease in the proband (MS-LCH and SS-LCH, OR = 21.6), and family history of thyroid disease (MS-LCH and SS-LCH, OR = 1.4). The association with thyroid disease in the proband was explained partially by the involvement of the pituitary, with the relative risk decreasing when patients with diabetes insipidus and thyroid involvement were excluded from analysis. CONCLUSIONS: This large hypothesis-generating study provides directions for future investigations in well-designed population-based or hospital-based epidemiologic studies.
Subject(s)
Histiocytosis, Langerhans-Cell/epidemiology , Adolescent , Canada/epidemiology , Case-Control Studies , Child , Child, Preschool , Female , Histiocytosis, Langerhans-Cell/classification , Histiocytosis, Langerhans-Cell/etiology , Humans , Infant , Male , Risk Factors , Socioeconomic Factors , Surveys and Questionnaires , United States/epidemiologyABSTRACT
The first major stride toward understanding LCH was taken when ultrastructural studies identified the proliferating cells as part of the Langerhans (dendritic) cell system. Another step forward was the definition of the morphologic, immunohistochemical, and clinical criteria needed for the diagnosis of LCH. Meanwhile, modern imaging studies have disclosed lesions that were not previously visible, especially those in the brain and the pituitary gland. These advantages have had a major impact on clinical management by making it possible to compare data from different institutions and to centralize coherent clinical and therapeutic data. Moreover, the agreement concerning diagnostic criteria provides a solid foundation for current clinical trials and for laboratory research regarding the possible roles of the immune system, clonality, and cytokines in the etiology of LCH.