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Erdheim-Chester disease (ECD) is a rare non-Langerhans cell histiocytosis characterised by long bones and various other organs’ involvements.1 Tissues are infiltrated by CD68+ CD1a− foamy histiocytes.2 Therapeutic options are pegylated interferon-α,3 cladribine,4 mTOR inhibitors5 and anakinra in mild forms of ECD.6 7 Conversely, targeted BRAF or MEK inhibitor therapies are used for refractory or life-threatening ECD manifestations.8 9 All these therapies have frequent side effects. Interferon-α leads to fatigue, cytopenias and autoimmune diseases. Anakinra needs subcutaneous daily injections, with frequent local intolerance. Targeted therapies cause skin cancers, QT allongement, rhabdomyolysis and haemorrhage,10 and we lack long-term safety data with these drugs. Moreover, targeted therapies are not available in all countries. Thus, there is an unmet need for improving treatments in many patients with ECD, particularly in countries where access to targeted therapies is complicated or impossible.
Although our comprehension of this disease has recently moved from inflammatory to clonal myeloproliferative disease,11 the accumulation of pathological histiocytes leads to an increase of several cytokines in blood and affected tissues. Cytokine/chemokine network has been described in ECD lesions, and most of these factors are regulated by tumour necrosis factor alpha (TNF-α), which is also expressed in ECD lesions and serous fluids like pericardial effusion12–14 and has been implicated in ECD pathogenesis in in vitro models.15 Two ECD patients with cardiovascular involvement were successfully treated with infliximab, a TNF-α monoclonal chimeric antibody, achieving an improvement of symptoms, cardiac involvement and function.14 We aim to determine the efficacy of infliximab in a larger series of patients with ECD.
We retrospectively reviewed …
Handling editor Josef S Smolen
Contributors FC-A, ZA and JH designed the study. FC-A, J-FE, NB, FC, PM and JH collected the data. J-FE and FC centrally reviewed the histological samples. J-FE determined the BRAF status. FC-A and JH conducted the statistical analysis. FC-A, J-FE, FC, ZA, PM, PC and JH analysed and interpreted the data. PM centrally reviewed the PET-CT scans. FC-A, J-FE, ZA and JH wrote the manuscript. All authors critically reviewed and approved the final version of the manuscript.
Funding This research received no specific grant from any funding agency in the public, commercial or not-for-profit sectors.
Competing interests None declared.
Ethics approval CPP Ile de France III.
Provenance and peer review Not commissioned; externally peer reviewed.
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