Erdheim-Chester Disease

Bilateral, symmetric osteosclerosis of the metadiaphyses of the long bones of the lower limbs, with symmetric increased uptake on bone scan, is the near-pathognomonic skeletal pattern of Erdheim-Chester disease. This is a rare non-Langerhans cell histiocytosis, a proliferation of foamy histiocytes that are CD68-positive and CD1a, or Langerin, negative, which distinguishes it from Langerhans cell histiocytosis, and it is driven by MAPK-pathway mutations, most commonly BRAF V600E. Recognising the bone pattern matters because ECD is a multisystem and potentially life-threatening disease, so I would look for the characteristic extraskeletal features: periaortic sheathing, the coated aorta; perinephric infiltration, the hairy kidney, which can obstruct the ureters; central nervous system and orbital involvement; and pituitary involvement causing diabetes insipidus. I would investigate with PET, which is often more informative than CT or MRI in showing the widespread FDG-avid lesions, and with CT and MRI for the organ involvement, and I would confirm the diagnosis with a biopsy showing foamy CD68-positive, CD1a-negative histiocytes, often with Touton giant cells, together with BRAF and molecular testing. I would distinguish it from Langerhans cell histiocytosis, which is CD1a-positive with lytic punched-out lesions, and from other causes of osteosclerosis such as osteoblastic metastases. Management has been transformed by targeted therapy - BRAF inhibitors for BRAF V600E-mutant disease and MEK inhibitors for the MAPK pathway - delivered by a specialist multidisciplinary team, with interferon-alpha used historically. My orthopaedic role is mainly recognition and biopsy, and managing the bone pain.