Modern approach to diagnosis and treatment of histiocytic disorders

We observe heterogeneous clinical presentations and unpredictable course in histiocytoses, ranging from involvement limited to skin or bone, with an excellent prognosis, to a severe multi-system disease associated with a poor outcome. Most cases occur in children from birth to age 15. The diagnostic criteria include cellular morphology, cell surface and cytochemical markers and electron microscopic findings. The three most common forms of histiocytosis in children are Langerhans cell histiocytosis (LCH), Haemophagocytic Lymphohistiocytosis (HLH) and indolent sinus histiocytosis. LCH is characterized by proliferation of Langerhans cells and can lead to multi organ infiltration. CD1a glycoprotein and Birbeck granules are the two most specific tests for LCH. HLH comprises two different conditions: familial hemophagocytic lymphohistiocytosis (FHL)- the primary HLH on the basis of a genetic defect, and the secondary form with underlying diseases (infections, cancer, rheumatic diseases). The prevalence of HLH is 1.2 in every 1,000,000 children under the age of 15. The onset of FHL is usually early in life. Four gene defects in FHL (autosomal recessive) have been identified, which account for approximately 50% to 80% of the familial cases. Two of the genes, PRF1 and UNC13D, are responsible for the synthesis of proteins, perforin, and MUNC13-4. A third defect affects the Syntaxin 11 (STX11) gene and the fourth is the BIRC4 gene, which mutation is associated with deficiency of the X-linked inhibitor of apoptosis. There remains a considerable percentage of FHL patients with no known underlying gene defect. Chemo-immunotherapy and hematopoietic stem cell transplantation improve outcome.

Keywords: HISTIOCYTES – immunology; HISTIOCYTOSIS – clasification, immunology, pathology
Category: Review
Volume: Vol. 49, No 1, january - march 2005
Authors: S. Čulić
Reference work:

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