Abstract
Background: Erdheim-Chester Disease (ECD), a non Langerhans’ cell histiocytosis of orphan nature and propensity
for multi-systemic presentations, comprises an intricate medical challenge in terms of diagnosis, treatment and
complication management.
Objectives: The objectives are to report the clinical, radiological and pathological characteristics, as well as cardinal
therapeutic approaches to ECD patients and to provide clinical analyses of the medical chronicles of these complex
patients.
Methods: Patients with biopsy proven ECD were audited by a multi-disciplinary team of specialists who formed a
coherent timeline of all the substantial clinical events in the evolution of their patients’ illness.
Results: Seven patients (five men, two women) were recruited to the study. The median age at presentation was
53 years (range: 39 to 62 years). The median follow-up time was 36 months (range: 1 to 72 months). Notable ECD
involvement sites included the skeleton (seven), pituitary gland (seven), retroperitoneum (five), central nervous
system (four), skin (four), lungs and pleura (four), orbits (three), heart and great vessels (three) and retinae (one).
Prominent signs and symptoms were fever (seven), polyuria and polydipsia (six), ataxia and dysarthria (four), bone
pain (four), exophthalmos (three), renovascular hypertension (one) and dyspnea (one). The V600E BRAF mutation
was verified in three of six patients tested. Interferon-α treatment was beneficial in three of six patients treated.
Vemurafenib yielded dramatic neurological improvement in a BRAF mutated patient. Infliximab facilitated pericardial
effusion volume reduction. Cladribine improved cerebral blood flow originally compromised by perivenous lesions.
Conclusions: ECD is a complex, multi-systemic, clonal entity coalescing both neoplastic and inflammatory elements
and strongly dependent on impaired RAS/RAF/MEK/ERK signaling.
Keywords: Erdheim Chester, BRAF, NRAS, Vemurafenib, Interferon-α, Histiocytosis