Differences in the imaging of Erdheim-Chester disease using FDG-PET/CT, NaF-PET/CT examinations, and skeletal scintigraphy. Regression of the disease after treatment with cladribine combined with cyclophosphamide and anakinra

BACKGROUND: Erdheim-Chester disease (ECD) is a rare disorder characterized by infiltrates of foamy histiocytes (histiocytes with abundant lipid inclusions - foamy cells) and inflammatory stroma, which induce a systemic inflammatory response. The disease typically infiltrates the bones causing osteosclerotic and mixed lesions with the characteristic "hot knees" pattern - increased uptake of radiopharmaceuticals in the epiphyses of bones near the knee joint. OBSERVATION: The patient had histologically confirmed ECD with negative test results for mutations in the BRAF gene and MEK pathway, but with aberrant cyclin D1 expression. The disease manifested with retrobulbar infiltrates, pericardial effusion, infiltration of the pancreas, retroperitoneum, and nerve roots. Secretion from the pericardial drain decreased after administration of high doses of methylprednisolone, followed by regular applications of anakinra. Extent of the disease was assessed by MRI of the head, PET/CT with the radiopharmaceuticals fluorodeoxyglucose (FDG) and sodium fluoride (NaF), and skeletal scintigraphy. FDG accumulated significantly in pathological infiltrates visible on low-dose CT. A pathological lesion with increased FDG accumulation was also present in the pituitary gland. FDG also showed increased accumulation in the bones, but the typical "hot knees" pattern was not present. This pattern, however, was visible on skeletal scintigraphy, and osteosclerotic lesions were most precisely detected using NaF-PET/CT. Treatment with interferon-alpha was unsuccessful. For second-line treatment, cladribine was used - in the first two cycles as monotherapy, and in the third and fourth cycles in combination with a low dose of cyclophosphamide. After the fourth cycle, symptoms of the disease regressed, and FDG-PET/CT showed disappearance or a significant reduction of pathological FDG accumulation in the disease lesions. Cladribine will be administered for a maximum of six cycles. CONCLUSION: FDG-PET/CT is currently the most appropriate examination for determining the extent of the disease as well as for assessing treatment response. However, the extent of osteosclerotic lesions, including the characteristic "hot knees" pattern, is more accurately visualized using NaF-PET/CT. Cladribine is an effective drug for both Langerhans cell histiocytosis and ECD. The therapeutic effect of cladribine, as well as its side effects, can be enhanced by adding cyclophosphamide. The inflammatory reaction induced by ECD was suppressed with anakinra.