Background

Rheumatologists are often confronted with systematic and rare diseases. Even among the rare diseases, clinical features may overlap, but treatment options for different diseases may differ.

Objectives

To illustrate the diagnostic challenges the clinician is confronted with when facing rare and systemic diseases in clinical practice with a case report where clinical features were overlapping.

Methods

A 64-year-old woman was presented to our institution after suffering from two ischemic strokes. Cerebral imaging was suggestive of large-vessel vasculitis. Additionally, imaging also revealed a left-sided retro-orbital mass. Her past medical history was notable for retroperitoneal fibrosis with ureteral obstruction requiring percutaneous drainage six months before presentation and placement of a cardiac pacemaker several years ago. Treatment with high-dose prednisone had been initiated but showed no clinical or laboratory improvement.

Results

Clinical examination revealed mild persistent facial hemiparesis and difficulty with ambulation. Mild exophthalmos was present on her left side. On palpation, there were palpable axillary masses bilaterally. Otherwise, her physical examination was normal. Laboratory analysis revealed elevated soluble interleukin-2 receptor levels at 2800 IU/mL (N: 230–770 IU/mL) and mildly increased C-reactive protein at 10 mg/L (N: <5 mg/L). Autoantibodies, including rheumatoid factor, IgG4, ANCA, ANA, and ENA were all within normal range. Plasma cells were normal on flow cytometric analysis. A PET-CT was performed which revealed signs of alveolitis, retroperitoneal fibrosis, axillary masses with strong tracer uptake (figure 1) as well as tracer uptake of the left femur and periaortic sheathing. We performed a biopsy of the left-sided axillary mass. Histopathologic analysis showed Touton giant cells and septal fibrosis. Staining was negative for CD1a and S100 but positive for CD68. Molecular pathologic analysis revealed the presence of the BRAFV600E mutation, findings that are consistent with the diagnosis of Erdheim-Chester disease. We initiated treatment with the BRAF-inhibitor vemurafenib and will follow the patient closely. Staining for IgG4 was negative.

Conclusions

Erdheim-Chester disease (ECD) and IgG4-related disease are very rare disorders and can present with similar clinical findings, such as retroperitoneal fibrosis, alveolitis or lymph node enlargement. About 500 cases of ECD worldwide have been reported. ECD is a non-Langerhans cell histiocytosis with a reported five-year survival rate of about 68%. Roughly 50% of patients show a BRAF mutation. Various treatment options have been reported and are recommended by the recently published consensus guidelines (1). These include interferon-alpha, vemurafenib and also TNF-alpha inhibitors, such as infliximab, but also interleukin-antagonists, such as anakinra (IL-1) or tocilizumab (IL-6). Rheumatologists have to consider non-Langerhans cell histiocytoses in the differential of systemic diseases because the distinction can be difficult and imaging, as well as meticulous histopathologic analyses, are necessary to correctly diagnose these patients because treatment differs.

References

Diamond EL et al. Consensus guidelines for the diagnosis and clinical management of Erdheim-Chester disease. Blood 2014 Jul 24;124(4):483–92.

Disclosure of Interest

None declared

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