A 65 yo male with a history of juvenile idiopathic arthritis presents with a three month hx of recurrent pericardial effusions.

and something wrong with his bones

 Pet scan showing uptake in the distal femurs.

Pet scan showing uptake in the distal femurs.

 and infiltration of the retroperitoneum with bilateral hydronephrosis

and infiltration of the retroperitoneum with bilateral hydronephrosis

 and something infiltrating his pituitary on MRI; what disease does he have?

and something infiltrating his pituitary on MRI; what disease does he have?

Our patient had Erdheim-Chester disease.  This is a rare form of non Langerhan’s cell histocytosis in which histiocytes( tissue macrophages) proliferate in  the entire body with predilection for :  marrow, pericardium, bones, pituitary and lung. The histiocytes are lipid laden and can form nodules in the tissues with fibrosis surrounding.   It was first described in 1930 by William Chester during his visit to the Austrian pathologist Jakob Erdheim in Vienna.

The disease usually occurs in middle-aged patients and can manifest in a variety of ways.  Manifestations run the gamut between a focal asymptomatic process where patients can present  only with leg pain (from  metaphyseal sclerosis) to a fatal systemic disease that involves all organ systems. About half of the patients diagnosed have multifocal disease:  fever, orbital tumors, lung fibrosis, pericardial infiltration, pituitary involvement or urinary tract obstruction from retroperitoneal fibrosis .

 our patient had been treated for chf for many weeks based on this cxr

our patient had been treated for chf for many weeks based on this cxr

A key to the diagnosis can be the infiltration of the pituitary although Inflammatory, infectious, granulomatous and neoplastic diseases of the pituitary can also cause pituitary infiltration. Tuberculosis, sarcoid, lymphoma and lymphocytic hypophysitis  (which has been linked to autoimmune disease) are common causes.

 Diseases causing pituitary infiltration

Diseases causing pituitary infiltration

Previous options included steroids or interferon, but half of the patients have point mutations of the BRAF gene at codon 600 substituting glutamine for valine.  Vemurafenib, which has been approved to treat the BRAF mutation for melanoma, also works for Erdheim-Chester disease and is currently the treatment of choice. Our patient is currently undergoing testing to see if he has the BRAF mutation. It is not clear if years of immune suppression led to the mutation. 

 

Haroche J, Cohen-Aubart F, Emile JF, ArnaudL, Maksud P, et al. Dramatic efficacy of vemurafenib in both multisystemiC and refractory Erdheim-Chester disease harboring the BRAF V600E mutation. Blood 121(9))1495-500.

Erdheim-Chester disease at the United States National Library of Medicine http://www.nlm.nig.gov/cgi/mesh/2003/MB-cgi?term=ERDHEIM-CHESTER=DISEASE.

 Verdalles U, Goicoechea M, Garcia de Vinuesa S, et al. Erdheim-Chester disease: a rare cause of renal failure2007 Nephrol Dial Transplant. 22(6):1776-77.

Contemporary Endocrinology Vol 3.  McDermott, M. Diseases of the Pituitary: Diagnosis and Treatment, Edited by ME Wieman Humana Press, Inc., Totowa, NJ. 305

 foamy macrophages and fibrosis seen on biopsy

foamy macrophages and fibrosis seen on biopsy