Incidental Diagnosis of Erdheim–Chester Disease in a 42‐Year‐Old Man With Persistent Elevated ESR and Peri‐Ocular Xanthomas: A Case Report

ABSTRACT

Erdheim–Chester disease (ECD) is a rare non‐Langerhans cell histiocytosis characterized by multisystem involvement and frequent diagnostic delay due to nonspecific clinical manifestations. We report a 42‐year‐old asymptomatic man with persistently elevated erythrocyte sedimentation rate (ESR) detected during routine laboratory evaluation. Physical examination revealed bilateral peri‐ocular xanthomas. Multimodal imaging demonstrated bilateral perirenal soft‐tissue infiltration with a characteristic “hairy kidney” appearance on computed tomography, symmetric skeletal involvement on bone scintigraphy, and metabolically active lesions on ¹⁸F‐FDG PET/CT. Histopathological examination of a peri‐ocular xanthoma biopsy revealed CD68‐positive, CD1a‐negative foamy histiocytes, confirming the diagnosis of Erdheim–Chester disease. Given the patient's oligosymptomatic presentation and absence of critical organ involvement, a watch‐and‐wait strategy with close surveillance was adopted. This case highlights the diagnostic value of subtle clinical findings, such as isolated inflammatory marker elevation and peri‐ocular xanthomas, and emphasizes the importance of accessible tissue biopsy combined with characteristic imaging features for early diagnosis of ECD.

Key Clinical Message

Peri‐ocular xanthomas with unexplained, persistent ESR elevation should prompt consideration of Erdheim‐Chester disease—even in asymptomatic young adults. Early biopsy of this accessible lesion enables rapid, noninvasive diagnosis.

A 42‐year‐old man with persistent ESR elevation and peri‐ocular xanthomas was diagnosed with Erdheim–Chester disease via biopsy of the accessible cutaneous lesion, supported by characteristic “hairy kidney” imaging and symmetric skeletal uptake.

1. Introduction

Erdheim–Chester disease (ECD) is a rare clonal non‐Langerhans cell histiocytosis characterized by infiltration of tissues with lipid‐laden CD68‐positive, CD1a‐negative histiocytes and recurrent activating mutations in the MAP‐kinase signaling pathway, most commonly BRAFV600E [1, 2, 3]. Although traditionally considered a disease of the fifth to seventh decades, cases diagnosed in younger adults are increasingly recognized [4, 5].

The clinical spectrum of ECD is broad, ranging from incidental laboratory abnormalities to severe, life‐threatening multiorgan involvement, which contributes to a substantial diagnostic delay; the median time from symptom onset to diagnosis exceeds 2 years in many series [6, 7]. Characteristic radiologic features include bilateral symmetric osteosclerosis of long bones, perirenal soft‐tissue infiltration producing the “hairy kidney” sign, and cardiovascular involvement such as the “coated aorta” [8, 9, 10].

Cutaneous manifestations, particularly peri‐ocular xanthomas or xanthelasma‐like lesions, occur in up to 20% of patients and represent an underutilized diagnostic opportunity [11, 12]. In parallel, nonspecific inflammatory markers such as isolated ESR elevation are common but rarely prompt early consideration of histiocytic disorders [13, 14]. We report an oligosymptomatic case of ECD diagnosed through recognition of these subtle clues.

2. Case History and Examination

A 42‐year‐old man was referred for evaluation of persistently elevated erythrocyte sedimentation rate (ESR), ranging from 50 to 80 mm/h, identified during routine health screening. The patient was asymptomatic and denied fever, weight loss, night sweats, bone pain, polyuria, or polydipsia. There was no significant past medical history or family history of rheumatologic, endocrine, or malignant disease.

Physical examination revealed normal vital signs and unremarkable cardiopulmonary and abdominal findings. The only abnormality was bilateral peri‐ocular xanthomas that had been present for approximately 6 months (Figure 1).

FIGURE 1.

Bilateral peri‐ocular xanthomas in a 42‐year‐old male with Erdheim–Chester disease.

3. Differential Diagnosis, Investigations, and Treatment

Initial laboratory investigations were otherwise unremarkable (Table 1).

TABLE 1.

Initial laboratory tests.

Parameter	Value	Unit	Parameter	Value	Unit
WBC	5220	/mm3	FBS	88	mg/dL
Hb	14	g/dL	2hpp	96	mg/dL
MCV	85.1	fL	Urea	20	mg/dL
RBC	4.35	×106/mm3	Cr	0.7	mg/dL
Platelet	241	×103/mm3	Uric Acid	4.2	mg/dL
Neutrophil	47	%	Na	137	mmol/L
Monocyte	11.5	%	K	4	mmol/L
Eosinophil	3.4	%	Ca	9	mg/dL
Basophil	0.6	%	P	3.2	mg/dL
Cholesterol	165	mg/dL	Mg	2.2	mg/dL
Triglyceride	105	mg/dL	AST	16	U/L
HDL	47	mg/dL	ALT	15	U/L
LDL	103	mg/dL	ALK	87	U/L
Ferritin	15	ng/mL	TSH	1.5	mIU/L
Folic Acid	10	ng/mL	T4	8.1	μg/dL
Vitamin B12	771	pg/mL	Vitamin D3	27	ng/mL
CRP	2	mg/L

Extensive rheumatologic and infectious evaluations yielded negative results. Abdominal ultrasonography demonstrated mild bilateral hydronephrosis without evidence of obstruction or renal parenchymal disease.

Given the unexplained persistent elevation of ESR, ¹⁸F‐FDG PET/CT was performed, demonstrating bilateral renal cortical FDG uptake, perirenal fat stranding, and a small left adrenal nodule with faint FDG uptake below hepatic background (Figure 2). PET/CT has been shown to be valuable in identifying metabolically active disease and guiding biopsy site selection in ECD [10, 15, 16].

FIGURE 2.

18F‐FDG PET/CT scan showing bilateral renal cortical uptake and perinephric fat stranding in Erdheim–Chester disease.

Subsequent contrast‐enhanced abdominal CT with an adrenal protocol revealed symmetric perirenal soft‐tissue infiltration sparing the renal parenchyma, producing the characteristic “hairy kidney” appearance highly suggestive of ECD (Figure 3) [8, 9]. The classic “coated aorta” sign was not observed, consistent with reports that radiologic phenotypes may be incomplete [17].

FIGURE 3.

Contrast‐enhanced abdominal CT showing bilateral perirenal soft‐tissue infiltration with preservation of renal parenchyma, producing the classic “hairy kidney” appearance characteristic of Erdheim–Chester disease.

Endocrine evaluation, including adrenal function testing, was normal (Table 2), excluding functional adrenal disease. Whole‐body ⁹⁹ᵐTc‐MDP bone scintigraphy demonstrated symmetric diaphyseal uptake in the long bones and axial skeleton (Figure 4), a pathognomonic feature of ECD [17, 18]. Brain MRI showed no evidence of central nervous system involvement.

TABLE 2.

Secondary Laboratory findings (adrenal function tests).

Urine 24 h	Value (reference range)
Volume (mL)	2100
Creatinine (mg/day)	1350
Normetanephrine (μg/day)	414 (< 600)
Metanephrine (μg/day)	270 (< 350)
Urine Free Cortisol (μg/day)	19 (20–290)
Serum	Value (reference range)
Cortisol a (μg/dL)	0.58 (≤ 1.8)

^a After overnight dexamethasone suppression test.

FIGURE 4.

Whole‐body bone scan revealing diffuse skeletal uptake in Erdheim–Chester disease.

Given the presence of peri‐ocular xanthomas, a biopsy of one lesion was performed. Histopathology revealed diffuse dermal infiltration by foamy histiocytes and Touton giant cells. Immunohistochemistry showed strong CD68 positivity, weak S‐100 expression, and absence of CD1a staining (Figure 5A–E), confirming the diagnosis of Erdheim–Chester disease [18, 19].

FIGURE 5.

(A) Histomorphology of palpebral skin shows diffuse and nodular infiltrate of dominantly lipidized histiocytes admixed with some Touton‐like giant cells (H&E × 40 original magnification). (B) High scanning of Touton‐like giant cells with central nuclei and peripheral vacuolated cytoplasm (H&E × 200 original magnification). (C) CD68 immunoreaction highlighted lipidized histiocytes and giant cells. (D) Weak immunoreaction of some histocytes with S‐100. (E) CD1a shows negative immunoreaction of histiocytes in dermis but highlighted Langerhans cells in epidermis.

4. Results, Outcome, and Follow‐Up

After multidisciplinary consultation with hematology‐oncology, the patient was diagnosed with oligosymptomatic Erdheim–Chester disease without evidence of progressive or life‐threatening organ involvement. In line with current recommendations for asymptomatic or minimally symptomatic patients, systemic therapy was deferred in favor of close observation [1, 20].

A watch‐and‐wait strategy was initiated, with scheduled clinical, laboratory, and radiologic follow‐up every 3–6 months to monitor for disease progression, including skeletal symptoms, endocrine dysfunction, renal impairment, or cardiovascular and central nervous system involvement.

5. Discussion

ECD is a diagnostic challenge due to its rarity and protean manifestations. Although typically diagnosed in older adults, this case supports growing evidence that ECD can present in younger patients with minimal symptoms [4, 5]. Persistent elevation of inflammatory markers, particularly ESR, may be one of the earliest laboratory abnormalities [13, 14].

Cutaneous xanthomas are often dismissed as benign; however, peri‐ocular xanthomas have been increasingly recognized as a valuable diagnostic gateway in ECD [11, 12]. Their accessibility allows for low‐morbidity biopsy that reliably demonstrates the characteristic CD68‐positive, CD1a‐negative histiocytic infiltrate, obviating the need for invasive retroperitoneal or osseous biopsies [19, 21].

Imaging findings were pivotal in this case. The “hairy kidney” sign is highly specific for ECD and should prompt consideration of the diagnosis even in the absence of other classic features [8, 9]. The absence of a “coated aorta” underscores the heterogeneity of radiologic presentations [17]. Bone scintigraphy and PET/CT complemented CT findings by demonstrating characteristic skeletal involvement and metabolically active disease [10, 15, 16, 17].

Similar to reports by Vargas et al. and Gagliardo et al., our case emphasizes the role of incidental findings and accessible cutaneous biopsy in shortening diagnostic delay [14, 21]. Early diagnosis is increasingly important given the availability of targeted therapies directed at MAP‐kinase pathway mutations [1, 20].

6. Conclusion

Erdheim–Chester disease may present incidentally with minimal symptoms and nonspecific laboratory abnormalities. Persistent inflammatory markers combined with peri‐ocular xanthomas should prompt consideration of ECD. Early biopsy of accessible lesions and targeted multimodal imaging can facilitate accurate diagnosis while avoiding unnecessary invasive procedures.

Author Contributions

Mohammad Rahimi: writing – original draft, writing – review and editing. Alireza Ghanadan: formal analysis, investigation. Nooshin Shirzad: writing – review and editing. Mehrnaz Doostmohammadi: formal analysis. Mahboobeh Hemmatabadi: conceptualization, writing – review and editing.

Funding

The authors have nothing to report.

Ethics Statement

The study was exempt from Institutional Review Board approval under Tehran University of Medical Sciences policies as it involved retrospective analysis of anonymized clinical data.

Consent

Written informed consent was obtained for publication of this case report and accompanying images. Written informed consent was obtained from the patient.

Conflicts of Interest

The authors declare no conflicts of interest.

Rahimi M., Ghanadan A., Shirzad N., Doostmohammadi M., and Hemmatabadi M., “Incidental Diagnosis of Erdheim–Chester Disease in a 42‐Year‐Old Man With Persistent Elevated ESR and Peri‐Ocular Xanthomas: A Case Report,” Clinical Case Reports 14, no. 2 (2026): e71998, 10.1002/ccr3.71998.

Data Availability Statement

Data are available from the corresponding author upon reasonable request.