Miliary Pattern on Chest X-Ray: Differential Diagnoses
The most common causes of a miliary pattern on chest X-ray are miliary tuberculosis, hematogenous metastases (particularly thyroid, renal, and lung adenocarcinoma), fungal infections (histoplasmosis, blastomycosis), sarcoidosis, pneumoconioses (silicosis), and hypersensitivity pneumonitis. 1
Primary Differential Diagnoses
Infectious Etiologies
Miliary Tuberculosis
- Represents the classic cause of miliary pattern, though chest radiography identifies only 59-69% of proven cases with high specificity (97-100%) 2
- Nodules typically measure <3 mm in diameter in 90% of correctly identified cases, with profusion scores ranging from mild (45%) to severe (28%) 2
- Requires acid-fast bacilli cultures and histopathology showing caseating granulomas for definitive diagnosis 3
Fungal Infections
- Blastomycosis can present with diffuse miliary nodular pattern in endemic areas, representing endogenous disseminated reinfection that may be fatal without prompt treatment 4
- Histoplasmosis produces similar miliary patterns, particularly in immunocompromised hosts 1
- Documentation requires organism recovery from body fluids or tissue, as skin and serologic testing are unreliable 4
Malignant Etiologies
Hematogenous Metastases
- Lung adenocarcinoma can present with miliary pattern, occurring in both EGFR-positive and EGFR-negative tumors 5
- Thyroid and renal cell carcinomas are classic causes of miliary metastases 1
- Typically presents with rapid clinical deterioration over weeks to months 5
Non-Infectious Inflammatory Conditions
Sarcoidosis
- Miliary pattern occurs in <1% of sarcoidosis cases but can be radiographically identical to tuberculosis 3
- Diagnosis requires non-caseating granulomas on transbronchial biopsy, negative fungal and AFB cultures, and supportive bronchoalveolar lavage findings 3
- Demonstrates clinical and radiological remission under corticosteroid therapy 3
Pneumoconioses and Hypersensitivity Pneumonitis
- Silicosis and other occupational exposures produce characteristic miliary patterns 1
- Hypersensitivity pneumonitis from organic antigen exposure creates similar diffuse micronodular disease 1
High-Resolution CT Pattern Recognition
Distribution-Based Classification
Centrilobular Pattern
- Nodules spare the pleural surfaces and interlobular septa
- Suggests hypersensitivity pneumonitis or respiratory bronchiolitis 1
Perilymphatic Pattern
- Nodules distributed along bronchovascular bundles, interlobular septa, and pleural surfaces
- Characteristic of sarcoidosis and silicosis 1
Random Pattern
- Nodules distributed without relationship to secondary lobular structures
- Classic for hematogenous spread: miliary tuberculosis, fungal infections, and metastases 1
Critical Diagnostic Approach
Initial Evaluation
- Obtain high-resolution CT to characterize nodule distribution pattern (centrilobular vs. perilymphatic vs. random) 1
- Review occupational and travel history for endemic fungal exposures and pneumoconiosis risk 4
- Assess immunocompromised status, as this dramatically increases risk of disseminated infections 4
Tissue Diagnosis Requirements
- Bronchoscopy with transbronchial biopsy and bronchoalveolar lavage for histopathology, fungal cultures, and AFB cultures 3
- Histopathology distinguishes caseating granulomas (tuberculosis) from non-caseating granulomas (sarcoidosis) 3
- Multiple negative cultures are required before excluding infectious etiologies 3
Common Pitfalls
Misdiagnosis of Sarcoidosis as Tuberculosis
- Miliary sarcoidosis is frequently misdiagnosed and empirically treated as tuberculosis due to radiographic similarity 3
- Always obtain tissue diagnosis before initiating anti-tuberculous therapy in stable patients 3
Chest Radiography Limitations
- Chest X-ray misses 31-41% of proven miliary tuberculosis cases, necessitating high clinical suspicion despite negative radiographs 2
- High-resolution CT is mandatory when clinical suspicion is high but chest X-ray is non-diagnostic 1
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