Summary. Langerhans cell histiocytosis (LCH) is considered a non-hereditary disorder. Evaluation of the few familial cases might provide insight into its aetiology and pathogenesis. We conducted a survey to identify familial LCH cases. Data on family history, zygosity assessment in twins, clinical and laboratory features, treatment outcome, and present status were collected. According to variable con®dence for twins monozygosity assessment, we termed these pairs`presumed monozygotic' (pMZ). Nine families had more than one affected relative: ®ve with LCH-concordant twin pairs, four with LCH in siblings or cousins. Three twin pairs not concordant for LCH were also studied. Overall, four of ®ve pMZ twin pairs and one of three dizygotic (DZ) pairs were concordant for LCH. The pMZ twins had simultaneous and early disease onset (mean age 5´4 months); onset was at 21 months in the DZ pair. Clinical features were similar in the pMZ pairs. One pair of DZ twins had disseminated LCH. The three healthy twins (one pMZ, two DZ) remain asymptomatic 0´3, 5´9 and 4´7 years, respectively, after disease onset in their co-twins. Of the two families with affected non-twin siblings, one had known parental consanguinity and the other possible consanguinity. Potential consanguinity was also present in one of the two families with affected ®rst cousins. Our data support high LCH concordance rates in pMZ twins and add the ®nding of LCH concordance in one of three dizygotic pairs studied. Taken together with our identi®cation of LCH in siblings and ®rst cousins from known or possibly consanguineous families, and with prior reports of three affected parent±child pairs, the data support a role for genetic factor(s) in LCH. The work-up of newly diagnosed patients should include a careful, extensive family history and chromosome studies. When possible, constitutional and/or lesional DNA should be obtained for future study.

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Leukotrienes (LTs) are recognized to be important mediators in asthma. Recent studies revealed that LT synthesis is controlled by the regulation of LT-synthesizing enzymes. We determined the synthesis of LTB4 and LTC4 by specific radioimmunoassay, and the messenger RNA (mRNA) expression of LT-synthesizing enzymes by reverse transcriptase polymerase chain reaction in peripheral polymorphonuclear leukocytes, which were obtained from controls and asthmatic children. The synthesis of LTB4 and LTC4, and the mRNA expression of 5-lipoxygenase, LTA4 hydrolase, and LTC4 synthase were enhanced in the patients. The mRNA expression of LT-synthesizing enzymes was up-regulated, resulting in increased LT synthesis, which may play an important role in the pathogenesis of childhood asthma.