From the Guidelines
Erdheim-Chester Disease (ECD) is a rare non-Langerhans cell histiocytosis that requires a comprehensive treatment approach, with BRAF-inhibitors such as vemurafenib or dabrafenib being first-line options for BRAF V600E-positive patients, and interferon-alpha, anakinra, or MEK inhibitors being considered for BRAF-negative cases, as recommended by the most recent consensus guidelines 1.
Clinical Manifestations
ECD primarily affects adults in their 50s-60s with a slight male predominance, and involves infiltration of tissues by foamy histiocytes that are CD68+, CD163+, Factor XIIIa+, but CD1a- and S100- 1. Clinical manifestations vary widely depending on organ involvement, with the most common being:
- Bone pain (particularly in the lower limbs)
- Diabetes insipidus from pituitary involvement
- Exophthalmos
- Xanthelasma
- Cardiovascular disease
- Retroperitoneal fibrosis
- Pulmonary infiltrates
Diagnosis
Diagnosis requires histopathological confirmation with immunohistochemistry showing the characteristic histiocyte profile, along with clinical and radiological findings such as bilateral symmetric osteosclerosis of long bones on X-ray or CT 1.
Treatment
Treatment depends on disease extent and BRAF mutation status. For BRAF V600E-positive patients, vemurafenib (960mg twice daily) or dabrafenib (150mg twice daily) combined with trametinib (2mg once daily) are first-line options 1. For BRAF-negative cases, interferon-alpha (3 million units 3 times weekly), anakinra (1-2mg/kg/day), or MEK inhibitors like cobimetinib (60mg daily) may be used 1. Severe cases may require chemotherapy with cladribine or high-dose corticosteroids.
Prognosis
Prognosis has improved with targeted therapies, but ECD remains a chronic disease requiring long-term management and multidisciplinary care due to its multisystem involvement 1.
From the Research
Overview of Erdheim-Chester Disease
- Erdheim-Chester disease (ECD) is a rare form of non-Langerhans cell histiocytosis, characterized by the infiltration of foamy histiocytes into various organs and tissues 2, 3, 4, 5, 6.
- The disease typically affects adults between their 5th and 7th decades of life, with males and females being almost equally affected 2.
- The etiology of ECD is unknown, but it is thought to be associated with an intense TH1 immune response and may be linked to the V600E BRAF mutation, which has been found in up to half of patients in recent studies 2, 5.
Clinical Manifestations
- The most common presenting symptom of ECD is bone pain, and the disease can affect various organs and systems, including the skeleton, central nervous system, cardiovascular system, lungs, kidneys, and skin 2, 3, 5.
- Patients with ECD may experience a range of symptoms, including fever, polyuria and polydipsia, ataxia and dysarthria, exophthalmos, renovascular hypertension, and dyspnea 3, 5.
- The disease can also cause significant morbidity due to histiocytic infiltration of critical organ systems, and the 5-year survival rate is approximately 68% 2.
Diagnosis
- The diagnosis of ECD is established by the identification of CD68(+), CD1a(-) histiocytes within a biopsy specimen, and bilateral symmetric increased tracer uptake on 99mTc bone scintigraphy affecting the periarticular regions of the long bones is highly suggestive of the disease 2.
- Imaging examinations, such as CT and PET/CT scans, can also help detect typical osteosclerotic changes and fibrotic changes in the affected organs 3, 5.
Treatment
- Interferon-α is the most extensively studied agent in the treatment of ECD and serves as the first line of treatment, with high-dose IFNα being effective in up to 67% of patients 2, 4, 6.
- Other treatment options, such as cladribine, anakinra, and vemurafenib, have shown promise in patients who do not respond to interferon-α, and may be used as second-line treatments 2, 3, 5.
- The choice of treatment depends on the organs involved and the presence of the V600E BRAF mutation, and treatment should be individualized based on the patient's specific needs and response to therapy 5, 6.