Erdheim-Chester disease mimicking IgG4-related disease

Aortitis is a rare but critical manifestation of systemic inflammatory disease, most commonly associated with large-vessel vasculitides such as Takayasu arteritis and giant cell arteritis. When accompanied by multiorgan inflammation and fibrosis, it presents a broader diagnostic challenge that includes immune-mediated conditions such as immunoglobulin G4-related disease (IgG4-RD) and rare histiocytic neoplasms. While IgG4-RD is increasingly recognised due to improved diagnostic criteria and access to immunostaining, histiocytic neoplasms such as Erdheim-Chester disease (ECD) remain underdiagnosed. ECD is a clonal histiocytic neoplasm driven by mutations in the mitogen-activated protein kinase pathway, with multisystem tissue infiltration and inflammation. Unlike IgG4-RD, ECD is amenable to targeted therapies. We present a diagnostically challenging case of a middle-aged woman referred with presumed IgG4-RD following five months of progressive retroperitoneal fibrosis, bilateral ureteric obstruction, weight loss, and fatigue. Further investigation revealed aortitis involving major branches, interstitial lung disease, and adrenal and pituitary involvement, but notably without skeletal disease. Omental biopsy confirmed ECD, with a pathogenic MAP2K1 mutation detected. This case highlights the diagnostic complexity of bone-sparing ECD, a phenotype present in fewer than five percent of cases. Its clinical mimicry of vasculitis and other inflammatory disorders can obscure the underlying neoplastic process, delaying diagnosis and access to effective treatment. In patients with systemic inflammation and inconclusive serology, early consideration of ECD is essential to guide appropriate investigations and timely therapy.