Erdheim-Chester Disease (ECD) is a rare, non-Langerhans cell histiocytosis involving xanthogranulomatous infiltration of various organ systems. It is difficult to diagnose because of its heterogeneous and nonspecific clinical presentation. This case report follows the tortuous diagnostic journey of a 55-year-old female with ECD, who initially presented with bone pain and bilateral exophthalmos, did not respond to early treatment and later developed cardiac, pulmonary, renal, and central nervous system symptoms. In more than three years, several medical work-ups have been performed by several specialists with broad differential diagnoses that included autoimmune diseases, cancer and inflammatory or viral related diseases. Initial studies lacked consistency and were complicated by overlapping symptoms related to diseases such as rheumatoid arthritis, systemic lupus erythematosus, sarcoidosis, orbital lymphoma, and Grave’s disease. The diagnosis was determined following the lung biopsy results which showed characteristic histiocytes with CD68 positive, CD163 positive, CD1a negative, and lipid-laden histiocytes. These lung biopsy findings were corroborated by radiological manifestations of bilateral long bone osteosclerosis, pericardial disease, retroperitoneal fibrosis, and thickening of the pituitary stalk. Further investigations revealed the presence of a BRAF V600E mutation and this confirmed the diagnosis. The patient was then placed on Vemurafenib with impressive clinical response. This case illustrates the protean nature of ECD, and the need to have a high index of suspicion in patients with unexplained multi-system disease. Rapid tissue diagnosis is not only of relevance to the molecular profiling and accuracy of the diagnosis, but also to direct personalized therapy. Thus, ECD should be considered in the differential diagnoses of other widespread disease that consider patients with non-specific osteoarticular pain and systemic symptoms that have not been sufficiently justified by clinical and radiographic results.
Nguyen et al. (2025) studied this question.