Cladribine, cyclophosphamide, and anakinra combination induces regression in Erdheim-Chester disease, improving imaging markers.

Erdheim-Chester disease (ECD) is a rare, systemic inflammatory disorder characterized by infiltrates of foamy histiocytes and inflammatory stroma. It commonly affects bones, causing osteosclerotic lesions and the characteristic “hot knees” pattern of increased radiopharmaceutical uptake near the knee joint epiphyses. Current treatments, like interferon-alpha, often have limited efficacy, highlighting the need for alternative therapeutic strategies, especially for patients without common BRAF or MEK pathway mutations, where aberrant cyclin D1 expression might play a role.

This case report details a patient with histologically confirmed ECD who tested negative for BRAF and MEK mutations but showed aberrant cyclin D1 expression. Initial treatment involved high-dose methylprednisolone followed by regular anakinra to manage pericardial effusion. For second-line therapy, cladribine was administered for two cycles as monotherapy, then combined with a low dose of cyclophosphamide for an additional two cycles. Disease extent and treatment response were monitored using MRI, FDG-PET/CT, NaF-PET/CT, and skeletal scintigraphy.

Pre-treatment imaging revealed extensive disease, including retrobulbar infiltrates, pericardial effusion, and infiltration of the pancreas, retroperitoneum, and nerve roots. FDG-PET/CT showed significant FDG accumulation in pathological infiltrates, including a lesion in the pituitary gland, but did not display the typical “hot knees” pattern in bones. This characteristic pattern was, however, clearly visible on skeletal scintigraphy. > NaF-PET/CT proved most precise in detecting the osteosclerotic lesions, offering superior anatomical detail for bone involvement. Following four cycles of cladribine (two monotherapy, two combined with cyclophosphamide), the patient experienced a marked regression of disease symptoms. Post-treatment FDG-PET/CT scans demonstrated a significant reduction or complete disappearance of pathological FDG accumulation in the previously identified disease lesions, indicating a robust therapeutic response.