Diagnosis can often be difficult because of the rareness of ECD as well as the need to differentiate it from LCH. A diagnosis from neurological imaging may not be definitive. The presence of symmetrical cerebellar and pontine signal changes on T2-weighted images seem to be typical of ECD, however, multiple sclerosis and metabolic diseases must also be considered in the differential diagnosis. ECD is not a common cause of exophthalmos but can be diagnosed by biopsy. However, like all biopsies, this may be inconclusive. Video-assisted thoracoscopic surgery may be used for diagnostic confirmation and also for therapeutic relief of recurrent pericardial fluid drainage. Histology
Histologically, ECD differs from Langerhans cell histiocytosis (LCH) in a number of ways. Unlike LCH, ECD does not stain positive for S-100 proteins or Group 1 CD1a glycoproteins, and electron microscopy of cell cytoplasm does not disclose Birbeck granules. Tissue samples show xanthomatous or xanthogranulomatous infiltration by lipid-laden or foamy histiocytes, and are usually surrounded by fibrosis. Bone biopsy is said to offer the greatest likelihood of reaching a diagnosis. In some, there is histiocyte proliferation, and on staining, the section is CD68+ and CD1a-. Treatment
Current treatment options include:

Surgical debulking
High-dose corticosteroid therapy
Ciclosporin
Interferon-α
Chemotherapy
Vemurafenib. It would appear that approximately half these patients harbor point mutations of the BRAF gene at codon 600 substituting the amino acid glutamine for valine. Vemurafenib, an oral FDA approved targeted agent to the BRAF protein for melanoma, shows dramatic activity in patients Erdheim–Chester disease whose tumor contains the same mutation. In 2017 the US FDA approved vemurafenib for this indication.
Voxelotor, sold under the brand name Oxbryta, is a medication used for the treatment of sickle cell disease. Developed by Global Blood Therapeutics, voxelotor is the first hemoglobin oxygen-affinity modulator. Voxelotor has been shown to have disease-modifying potential by increasing hemoglobin levels and decreasing hemolysis indicators in sickle cell patients. It has a safe profile in sickle cell patients and healthy volunteers, without any dose-limiting toxicity.In November 2019, voxelotor received accelerated approval in the United States for the treatment of sickle cell disease (SCD) for those twelve years of age and older. The U.S. Food and Drug Administration (FDA) considers it to be a first-in-class medication. In December 2021, voxelotor received accelerated approval in the United States for the treatment of sickle cell disease (SCD) for those aged four to eleven years. Side effects
Common side effects include headache, diarrhea, abdominal pain, nausea, fatigue, rash and pyrexia (fever). History
Voxelotor was granted accelerated approval by the U.S. Food and Drug Administration (FDA) in November 2019. The FDA granted the application for voxelotor fast track designation and orphan drug designation.The approval of voxelotor was based on the results of a clinical trial with 274 participants with sickle cell disease.The FDA granted the approval of Oxbryta to Global Blood Therapeutics.