Erdheim chester disease (ECD) (Blood 2014)

Intro

Rare, multisystem non-Langerhans histiocytosis

Described in 1930 but rapid increase in cases since 2000 due to greater awareness of disease

Delayed diagnosis common

Epidemiology

Male > Female

Age at diagnosis typically 40-70 y.o.

Pathophysiology

Previously considered a non-neoplastic inflammatory disorder but an increasing proportion of cases now shown to have BRAFV600E mutations —> ECD now better considered a cloncal neoplastic disorder with a characteristic inflammatory cytokine profile.

Hyperactivation of these inflammatory pathways contributes to the clinical syndrome of ECD.

Clinical Features

Almost any organ system can be involved, with symptoms resulting from tissue infiltration. The following are some more common presenting features, but is not an exhaustive list.

  • Bones - Knee pain common presenting feature

  • Cardiac - Pericarditis, effusions

  • Eyes - Exopthalmus and retro-orbital pain, diplopia

  • Resp - Pulmonary involvement may be asymptomatic

  • CNS - Meningeal lesions

  • Endo - Diabetes insipidus

  • Renal - Hydronephrosis

  • Skin - Xanthelasma

  • Psych - Disinhibition, depression

Diagnostic Investigations

Tissue biopsy - infiltration by foamy histiocytes with surrounding fibrosis, with a typical immunohistochemistry profile (CD68+, CD163+, CD1a-, Langerin-)

Radiology - symmetrical osteoscelorosis of distal femur almost always present (>90%) and dense perinephritic fat seen on CT, called ‘hairy kidney’, is common.

BRAF mutation - by immunohistochemistry or molecular testing.

Management

BRAF inhibitors - e.g. vemurafenib, dabrafenib - small numbers and short follow-up periods at present but appear capable of inducing complete responses and look promising for significant improvement in overall survival (JAMA Oncol 2018)

Interferon-alpha - reduces lesional burdern, overal survival benefit

Anticytokines - anakinra, infliximab, tocilizumab - effective for bone pain and consitutional symptoms

Prognosis

Pre-interferon availability: 32-month survival 43%

Interferon treatment: 5-year survival 68%

BRAF inhibitors: 2-year survival 96%