Erdheim-Chester disease presenting with multisystem involvement: A case report

Abstract

BACKGROUND

Erdheim-Chester disease (ECD) is an ultra-rare non-Langerhans cell histiocytosis driven by clonal proliferation of lipid-laden histiocytes. With fewer than a thousand documented cases globally, it remains largely unreported in South Asia.

CASE SUMMARY

A 46-year-old male presented with chronic leg pain, polyuria, and visual disturbances. Radiologic findings revealed symmetric osteosclerosis of long bones and absent pituitary shadow with thickened stalk of pituitary gland. Histopathology showed foamy histiocytes positive for CD68 and CD163 but negative for CD1a and Langerin. Detection of BRAF V600E mutation confirmed the diagnosis. The patient was treated with corticosteroids and interferon-alpha, with significant symptomatic improvement at six months.

CONCLUSION

This case represents the first case of ECD reported from Pakistan. Awareness of its distinct imaging and histologic patterns can facilitate diagnosis even in resource-limited settings. National rare disease registries and access to molecular diagnostics are essential for improving outcomes.

Key Words: Erdheim-Chester disease; Non-Langerhans cell histiocytosis; Interferon-alpha; Multisystem disorder; Case report

Core Tip: Erdheim-Chester disease, a rare non-Langerhans histiocytosis, can mimic pituitary and other systematic on imaging. Recognition of its characteristic radiologic and immunohistochemical profile enables timely diagnosis and treatment in low-resource settings.

INTRODUCTION

Erdheim-Chester disease (ECD) is a rare clonal histiocytic neoplasm first described in 1930. It is characterized by infiltration of tissues by foamy, lipid-laden histiocytes that are CD68 and CD163 positive but CD1a and Langerin negative. The disease affects multiple organ systems, including the skeleton, retroperitoneum, cardiovascular system, and central nervous system. Global incidence is estimated at fewer than one per million, with a slight male predominance and peak presentation between 40 years and 70 years of age[1,2].

Advances in molecular profiling have identified mutations in the mitogen-activated protein kinase (MAPK) pathway, primarily BRAF V600E, in nearly two-thirds of cases[3]. These discoveries have shifted ECD’s classification from an inflammatory disorder to a neoplastic disease and opened the door for targeted therapies such as vemurafenib[4].

Despite global awareness, ECD remains underdiagnosed in low- and middle-income countries like Pakistan, where advanced molecular and immunohistochemical diagnostics are limited. This case likely represents the first histologically and molecularly confirmed instance of ECD reported from Pakistan. It highlights how recognition of characteristic radiologic and pathologic features can enable diagnosis even in settings without full access to genomic testing.

CASE PRESENTATION

Chief complaints

A 46-year-old male, school teacher by profession a resident of Lahore presented to the outpatient clinic with progressive dull pain in both legs for 18 months, associated with increased thirst, polyuria, and nocturia for one year, and recent blurring of vision over four months.

History of present illness

There was no history of fever, night sweats, tuberculosis exposure, or autoimmune illness.

History of past illness

Unremarkable.

Personal and family history

The patient had no significant family history and denied consanguinity.

Physical examination

Physical examination revealed mild right-sided proptosis, tenderness along the tibial shafts, and dry skin. No lymphadenopathy, hepatosplenomegaly, or cardiac murmurs were detected. The remainder of the systemic examination was unremarkable.

Laboratory examinations

Initial laboratory workup showed mild normocytic anemia (hemoglobin 12.3 g/dL) and elevated erythrocyte sedimentation rate (72 mm/hour). Serum sodium was slightly elevated (147 mmol/L), and urine osmolality was low (160 mOsm/kg), suggesting central diabetes insipidus. Autoimmune serology (antinuclear antibody, anti-neutrophil cytoplasmic antibodies) and infectious panels (human immunodeficiency virus, hepatitis B/C, syphilis) were negative.

Imaging examinations

X-rays of both lower limbs demonstrated bilateral, symmetric, osteosclerosis of the metaphyseal-diaphyseal regions (“candle wax” appearance) as shown in Figure 1.

Figure 1 X-ray bilateral legs. A and B: Anterior and lateral view showing bilateral, symmetric, osteosclerosis of the metaphyseal-diaphyseal regions (“candle wax” appearance) (arrows).

Magnetic resonance imaging (MRI) of the brain showed thickened pituitary stalk and loss of the posterior pituitary bright spot as shown in Figure 2. An open biopsy of the perirenal tissue via computed tomography (CT)-guided biopsy showed dense infiltration of foamy histiocytes with scattered Touton-type giant cells in a fibrotic stroma. Immunohistochemical analysis demonstrated positivity for CD68 and CD163 but negativity for CD1a and Langerin, confirming a non-Langerhans histiocytosis. PCR-based mutation analysis performed in an external laboratory detected BRAF V600E mutation, confirming ECD.

Figure 2 Sagittal view of magnetic resonance imaging brain. A: Sagittal view of magnetic resonance imaging (MRI) brain showing absent pituitary shadow and thickened stalk; B: Coronal view of MRI brain showing absent pituitary shadow and thickened stalk.

FINAL DIAGNOSIS

The following are diseases for differential diagnosis: ECD; Langerhans cell histiocytosis; sarcoidosis; immunoglobulin G4-related disease; idiopathic retroperitoneal fibrosis.

The definitive diagnosis was established on the basis of immunological and histopathological testing. The key distinguishing feature of ECD is its unique immunophenotype-it is CD1a- and Langerin-negative, which differentiates it from Langerhans cell histiocytosis, and it often harbors a BRAF V600E mutation, helping to distinguish it from sarcoidosis. The final diagnosis is ECD.

TREATMENT

The patient was started on oral prednisolone (40 mg/day, tapered) and subcutaneous interferon-alpha (3 million IU, thrice weekly). Desmopressin nasal spray was initiated for central diabetes insipidus.

OUTCOME AND FOLLOW-UP

At six months’ follow-up, the patient reported improved bone pain and reduced polyuria, with CT showing partial regression of perirenal infiltration and stable skeletal sclerosis.

DISCUSSION

ECD represents a histiocytic neoplasm within the L-group histiocytoses, characterized by chronic inflammation and tissue infiltration by foamy macrophages. The condition has a striking male predominance and can involve virtually any organ, leading to highly variable clinical presentations[1-3].

The skeletal system is affected in over 90% of patients, typically manifesting as bilateral symmetrical osteosclerosis of long bones, as seen in this patient. Extra-skeletal involvement, particularly in the retroperitoneum, cardiovascular system, and central nervous system, occurs in nearly 60% of cases and determines prognosis[4].

Histopathologically, ECD lesions consist of lipid-laden histiocytes surrounded by fibrosis. The immunophenotype-CD68 and CD163 positive but CD1a and Langerin negative-distinguishes ECD from Langerhans Cell Histiocytosis[2]. The detection of BRAF V600E or other MAPK pathway mutations confirms the clonal nature of the disease[3].

The major challenge in Pakistan is the lack of diagnostic infrastructure, including immunohistochemistry panels and molecular testing for BRAF mutations. Consequently, ECD may be mistaken for idiopathic retroperitoneal fibrosis or granulomatous infections such as tuberculosis, which are far more prevalent. Recognition of characteristic radiologic features can therefore serve as a critical diagnostic clue in resource-limited settings[5].

Treatment strategies depend on mutation status and organ involvement. Targeted therapy with vemurafenib (for BRAF-mutant ECD) has transformed survival outcomes, achieving response rates exceeding 80%[1,6]. However, access to these agents is limited in Pakistan due to cost and regulatory barriers. Interferon-alpha remains a viable option and can stabilize disease in the absence of targeted therapy. Corticosteroids provide short-term symptomatic relief but do not alter long-term outcomes[5,6].

This case illustrates how strategic clinical suspicion, imaging correlation, and basic immunohistochemistry can lead to correct diagnosis even without advanced molecular facilities. Establishing regional referral centers for histiocytic disorders and collaborative links with international molecular laboratories could improve detection and management of rare diseases in Pakistan.

CONCLUSION

This report describes what is likely the first histologically and molecularly confirmed case of ECD in Pakistan. It demonstrates the value of combining radiologic pattern recognition with focused immunohistochemistry for diagnosis in resource-constrained environments. Broader clinician awareness, diagnostic networking, and the creation of a Pakistan Rare Disease Registry are essential steps toward improving care for patients with histiocytic neoplasms.