Erdheim-Chester disease D76.3

Rare (1500 cases have been reported worldwide since 1930/Haroche J et al. 2020), formerly attributed to disseminated adult xanthogranulomas(non-Langerhans cell histiocytosis), which according to recent findings (overlap between Langerhans cell histiocytoses and Erheim-Chester disease is found in 20% of cases) is assigned to the Langerhans group of histiocytoses (L group) in the 2016 classification (see below Histiocytoses).

The etiology is unknown. Inflammatory or neoplastic causes are discussed.

Detectable levels of interferon-alpha, interleukin-7, interleukin-12, and monocyte chemoattractant protein 1 (see CCL2) are elevated. Interleukin-4 is frequently decreased. The described constellation suggests a systemic, Th-1-oriented immune disorder.

Detection of mutations in the BRAF proto-oncogene(BRAFV600E) is detectable in > 50% of cases, making it an important diagnostic feature of the disease.

ECD becomes manifest in adults between 40 and 60 years of age; m:w = 3:1.

The clinical course of the disease is wide-ranging. It varies from asymptomatic to multisystemic, life-threatening forms.

Bone infiltration: The pathognomonic feature of ECD is osteosclerosis of the long bones(bone pain especially in the distal lower extremities (80-95% of cases). Infiltration of the pituitary gland leads to diabetes insipidus and in rare cases hyperprolactinemia and gonadotropin deficiency.

General symptoms: fever, generalized weakness and weight loss.

Ophthamologic: exophthalmos, papilledema.

Dermatologic changes (rather rare): clinically uncharacteristic skin-colored to yellowish papules, nodules and plaques, and xanthelasma.

CNS: demonstrable cerebellar and pyramidal signs, headache, seizures, cognitive impairment, cranial nerve palsies, and sensory disturbances. Central nervous system involvement is a strong (negative) prognostic factor!

Cardiovascular: Evidence of a so-called "coated aorta" (40% of cases). Alterations of the renal arteries lead to renal hypertension. Other inconstant symptoms include pericardial tamponade, pseudo-tumorous infiltration of the right atrium (36% of cases), and dyspnea due to infiltration of the lungs.

Pseudo-retroperitoneal fibrosis is sometimes complicated by bilateral hydronephrosis.

Diffuse to granulomatous accumulation of mostly xanthomatized macrophages, giant cells, and single eosinophilic granulocytes. Older lesions with a tendency to fibrosis. Cells were negative for CD1a and CD207 but positive for CD68. S100 protein was detected sporadically.

Sarcoidosis

Whipple's disease

Langerhans cell histiocytoses of other provenance

Interferon-α appears to be the best first-line treatment for ECD. Since 2012, more than 200 patients with multisystemic or refractory ECD worldwide have benefited from highly effective therapy with BRAF and MEK inhibitors. Targeted therapies have overall, robust, and reproducible efficacy in ECD, with no acquired resistance to date. However, their use is best reserved for the most severe manifestations of the disease, as they may be associated with serious adverse effects and as yet unknown long-term consequences.

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