Abstract Introduction Hypereosinophilic syndrome (HES) is a rare multisystem disorder characterized by sustained eosinophilia (1.5 × 109/L) with evidence of organ involvement and absence of secondary causes of organ damage. Dyspnea, cough and wheezing are common in lung involvement. Radiologic findings in HES may show nodules, ground glass opacities, interlobular septal thickening, or pleural effusion. The clinical and radiographic features can be variable leading to diagnostic challenges. Here, we report a case of HES manifesting as ILD. Case Presentation A 67-year-old man with a past medical history including coronary artery disease, hypertension, and hyperlipidemia presented with chronic cough and progressive dyspnea. He was a former smoker (52 pack-years) and denied bird exposure, travel, or autoimmune disease. He reported no occupational exposure to asbestos, silica, coal dust, or other inhalational irritants; he works in storage shed sales.High-resolution computed tomography revealed ground-glass opacities, and traction bronchiectasis across all lung zones, with mediastinal and hilar lymphadenopathy. Laboratory studies showed marked eosinophilia (absolute eosinophil count 4.4 × 10³/µL) and elevated serum IgE (10,426 IU/mL). His hypersensitivity pneumonitis panel and Aspergillus-specific IgE were negative. Rheumatoid factor was elevated (315 IU/mL), while ANA, ANCA, anti-CCP, SSA/SSB, and complement levels were unremarkable. Myositis antibody testing was weakly positive for anti-NXP-2. Bronchoscopy with transbronchial cryobiopsy was performed. Histopathology showed chronic interstitial inflammatory cellular infiltrates and focal organizing pneumonitis with admixed eosinophils and epithelioid histiocytes. Acid-fast and fungal stains were negative. The 1,3-beta-D-glucan test and culture from bronchoalveolar lavage fluid were both negative. The infectious workup, including β-D-glucan and bronchoalveolar lavage cultures, was negative. Given persistent eosinophilia and evidence of pulmonary involvement, a diagnosis of HES-associated ILD was established. Prednisone 60 mg daily was initiated, resulting in marked symptomatic improvement and reduction of the eosinophil count to 0.2 × 10³/µL within one week. Discussion This case illustrates the diagnostic complexity of eosinophilic lung diseases. Although pulmonary involvement is frequent in HES, the presentation is heterogeneous, ranging from reversible infiltrates to progressive fibrosis. Comprehensive evaluation for primary and secondar causes of eosinophilia, including hematologic, infectious, allergic, and autoimmune etiologies is essential. In this patient, infectious and autoimmune studies were unrevealing, and hematologic evaluation is ongoing to exclude clonal or myeloproliferative variants. Early recognition and corticosteroid therapy are crucial to prevent irreversible fibrosis, while steroid-refractory disease may require cytotoxic or biologic agents targeting interleukin-5. This case emphasizes the need for a systematic, multidisciplinary approach when evaluating ILD with unexplained eosinophilia. This abstract is funded by: None
Phang et al. (Fri,) studied this question.