CARDIOVASCULAR RISK FACTORS IN ADULT PATIENTS WITH MULTISYSTEM LANGERHANS-CELL HISTIOCYTOSIS: EVIDENCE OF GLUCOSE METABOLISM ABNORMALITIES

CARDIOVASCULAR RISK FACTORS IN ADULT PATIENTS WITH MULTISYSTEM LANGERHANS-CELL HISTIOCYTOSIS: EVIDENCE OF ABNORMALITIES OF CARBOHYDRATE METABOLISM

Langerhans cell histiocytosis (LCH) is a rare disease, usually affecting children although it has recently increasingly been recognized in adults with a prevalence of approximately 1/560.000 cases ( , ). LCH is characterized by the aberrant proliferation of dendritic cells of the monocyte-macrophage system that resemble normal epidermal Langerhans' cells. These cells can infiltrate many sites of the body leading to either localized lesions or widespread systemic disease. Although LCH has been shown to be a clonal disorder ( ) it also exhibits features of an inflammatory disease, as altered expression of cytokines and cellular adhesion molecules important for the migration and homing of Langerhans cell has been documented ( , ). In addition, LCH shows a particular predilection for hypothalamo-pituitary axis (HPA) involvement leading to diabetes insipidus and/ or anterior pituitary dysfunction in 15-50% and 5-20%, of patients respectively (3, , , ). These percentages may be higher in adult patients with multisystem involvement, being 94% and 59% respectively ( ).

The ongoing inflammatory process and the presence of hypopituitarism are considered to be two independent risk factors for cardiovascular diseases probably through the induction of insulin resistance (IR) ( , , ). The various therapies used for the treatment of multisystem LCH, chemotherapy, radiotherapy and particularly glucocorticoids, may also adversely affect the cardiovascular system mostly through IR ( , ). It is therefore possible that patients with LCH represent a group at higher risk for cardiovascular diseases through the additive effect of a number of different contributing mechanisms known to induce IR. Insulin resistance besides producing an adverse metabolic profile can also lead to endothelial dysfunction and early vascular disease ( ). Early vascular disease can be detected by non-invasive surrogate markers, such as intima-media thickness (IMT) for vascular structure properties and flow-mediated vasodilatation (FMD) for vascular functional properties ( , , ). Carotid IMT is considered an established marker for early atherosclerotic disease and predictor of future cardiovascular events (16) whereas brachial artery FMD has been correlated with coronary endothelial function, a well-known predictor of future cardiovascular events (18).

Main outcome measures: Cardiovascular risk factors assessment were estimated in patients with LCH and compared to controls; the effect of hypopituitarism, disease activity and/ or treatment were determined.

SUBJECTS AND METHODS All patients have to fulfil the diagnostic criteria for "definitive diagnosis" of LCH ( ). Matched to sex, age, and BMI healthy individuals, in good health and not receiving any medication known to affect carbohydrate, sex hormone metabolism, and/or endothelial function for at least 3 months prior have also to be recruited for the study.