How to Differentiate ILD Types

Understanding interstitial lung disease (ILD) is akin to navigating a complex maze. It’s not a single condition, but a vast and varied group of over 200 distinct disorders, all characterized by inflammation and scarring (fibrosis) of the interstitium – the delicate tissue and space surrounding the air sacs (alveoli) of the lungs. For clinicians, accurately differentiating between these ILD types is paramount. A precise diagnosis dictates treatment strategies, predicts prognosis, and ultimately, significantly impacts a patient’s quality of life. Misdiagnosis, on the other hand, can lead to inappropriate therapies, accelerated disease progression, and unnecessary patient distress.

This comprehensive guide aims to demystify the process of differentiating ILD types, providing a detailed, actionable framework for healthcare professionals. We will delve into the diagnostic journey, exploring the crucial role of clinical assessment, advanced imaging, pulmonary function tests, serological markers, and the definitive power of lung biopsy. Each section will offer concrete examples and practical insights to enhance diagnostic accuracy and optimize patient care.

The Foundation: A Meticulous Clinical Assessment

The diagnostic journey for ILD invariably begins with a thorough and systematic clinical assessment. This initial phase is not merely about gathering symptoms; it’s about piecing together a holistic picture of the patient’s health, lifestyle, environmental exposures, and medical history.

Unraveling the Patient’s Story: History Taking

A detailed patient history is perhaps the most undervalued yet profoundly impactful tool in ILD differentiation. Every piece of information, no matter how seemingly insignificant, can serve as a crucial clue.

• Symptom Onset and Progression:
  • Gradual vs. Acute: Idiopathic pulmonary fibrosis (IPF) typically presents with insidious onset of shortness of breath and cough, worsening over months to years. In contrast, acute interstitial pneumonia (AIP) presents rapidly, often mimicking acute respiratory distress syndrome (ARDS). Hypersensitivity pneumonitis (HP) can have both acute presentations (following heavy, short-term exposure) and chronic forms (insidious onset with lower level, prolonged exposure).

  • Specific Triggers: Does dyspnea worsen with specific activities or in certain environments? This points strongly towards environmental exposures, a hallmark of HP. For instance, a farmer experiencing worsening cough and breathlessness during hay season, or an individual whose symptoms correlate with spending time with pet birds, immediately brings HP to the forefront.

  • Associated Symptoms: Beyond cough and dyspnea, look for constitutional symptoms like fatigue, weight loss, and low-grade fever, which can suggest systemic inflammatory diseases. Joint pain, skin rashes, Raynaud’s phenomenon, and sicca symptoms (dry eyes, dry mouth) are red flags for connective tissue disease-associated ILD (CTD-ILD). Chest pain can be present in sarcoidosis or drug-induced ILD. Hemoptysis, while rare in most ILDs, might suggest diffuse alveolar hemorrhage syndromes.

• Occupational and Environmental Exposures: This is a critical line of inquiry, particularly for HP.

  • Specific Agents: Enquire about exposure to molds (e.g., Aspergillus in farmer’s lung, Thermoactinomyces vulgaris in bagassosis), bird antigens (pigeon breeder’s lung, bird fancier’s lung), metal dusts (berylliosis, hard metal disease), silica (silicosis), and asbestos (asbestosis).

  • Duration and Intensity: Chronic low-level exposure can lead to chronic HP, while acute heavy exposure can trigger acute HP.

  • Home and Work Environment: Ask about hobbies involving birds, damp basements, hot tubs, or specific industrial settings. A patient working in sandblasting, for example, would raise immediate suspicion for silicosis.

• Medication History: A meticulously detailed medication history is essential to rule out drug-induced ILD. Many medications, including amiodarone, methotrexate, nitrofurantoin, and certain biologics, can cause interstitial lung damage. The temporal relationship between drug initiation and symptom onset is key. Discontinuation of the offending agent often leads to improvement, though fibrosis can be irreversible.

• Family History: Certain ILDs, such as familial IPF, have a genetic predisposition. A family history of lung fibrosis or autoimmune diseases should prompt further investigation into genetic factors or CTD-ILD.

• Co-morbidities: Gastroesophageal reflux disease (GERD) is highly prevalent in IPF and can exacerbate cough. Obstructive sleep apnea (OSA) is also common. Other conditions like chronic kidney disease or liver disease might influence treatment choices.

The Art of Observation: Physical Examination

While often non-specific, a thorough physical examination can provide valuable clues and corroborate historical findings.

• Auscultation of Lungs:
  • Velcro Crackles: Fine, inspiratory, non-postural crackles, often described as “Velcro rales,” are a hallmark of IPF and other fibrotic ILDs, particularly at the lung bases. Their presence suggests established fibrosis.

  • Wheezing: While not typical for most ILDs, wheezing might indicate concomitant airway disease or, in rare instances, be present in hypersensitivity pneumonitis or sarcoidosis affecting airways.

  • Squeaks: Inspiratory squeaks, sometimes heard in HP, are thought to be due to small airway disease.

• Clubbing of Digits: Digital clubbing, characterized by an increased nail bed angle and spongy nail beds, is a common sign of chronic hypoxemia and is frequently observed in IPF (in up to 50-60% of patients) and other fibrotic ILDs. Its absence, however, does not rule out ILD.

• Extrapulmonary Manifestations: These are critical for identifying CTD-ILD.

  • Skin: Rashes (e.g., heliotrope rash, Gottron’s papules in dermatomyositis; sclerodactyly in systemic sclerosis), Raynaud’s phenomenon, and digital ulcers.

  • Joints: Swelling, tenderness, and deformity suggestive of arthritis.

  • Eyes/Mouth: Sicca symptoms indicative of Sjögren’s syndrome.

  • Cardiac: Signs of pulmonary hypertension (loud P2, right ventricular heave).

Illuminating the Lungs: Advanced Imaging

High-resolution computed tomography (HRCT) of the chest is the cornerstone of ILD diagnosis and differentiation. It provides detailed anatomical information about the lung parenchyma, revealing characteristic patterns that can narrow down the diagnostic possibilities.

The Power of HRCT Patterns

Specific HRCT patterns are highly suggestive of certain ILD types. While not always definitive on their own, they are invaluable when interpreted in conjunction with clinical data.

• Usual Interstitial Pneumonia (UIP) Pattern: This is the most specific pattern and, in the right clinical context (e.g., older male, progressive dyspnea, Velcro crackles), is highly suggestive of IPF.
  • Key Features:
    • Reticulations: A network of fine, linear opacities, primarily subpleural and basal.

    • Honeycombing: Clustered cystic airspaces, typically 2-10 mm in diameter, often with thick, well-defined walls. Honeycombing is considered definitive evidence of fibrosis and is crucial for a confident UIP diagnosis. It usually has a peripheral and basal predominance.

    • Traction Bronchiectasis/Bronchioloectasis: Dilatation of bronchi and bronchioles due to surrounding fibrotic pull.

    • Absence of Features Suggesting an Alternative Diagnosis: Lack of extensive ground-glass opacities, nodules, or prominent lobular distribution.

  • Distribution: Predominantly subpleural and basal. Often patchy, with normal lung interspersed.

• Nonspecific Interstitial Pneumonia (NSIP) Pattern: This pattern is less specific than UIP and can be seen in various ILDs, including CTD-ILD, drug-induced ILD, and chronic HP.

  • Key Features:
    • Ground-Glass Opacities (GGOs): Hazy increase in lung attenuation, often patchy or diffuse.

    • Reticulations: Similar to UIP but often less prominent and more diffuse.

    • Bronchiectasis/Bronchioloectasis: Less prominent than in UIP.

    • Absence of Honeycombing: Crucial for distinguishing from UIP.

  • Distribution: Often diffuse or subpleural, sometimes with mid-lung predominance.

• Hypersensitivity Pneumonitis (HP) Pattern: HP exhibits a wide spectrum of HRCT findings, depending on the acuity and chronicity of the exposure.

  • Acute/Subacute HP:
    • Centrilobular Nodules: Small (<5 mm), ill-defined, scattered centrilobular nodules, often with ground-glass attenuation. These represent bronchiolitis.

    • Ground-Glass Opacities: Patchy or diffuse, often with upper or mid-lung predominance.

    • Air-Trapping (on expiratory CT): Due to bronchiolar inflammation and obstruction, seen as patchy areas of lung with lower attenuation. This is a very important sign for HP.

  • Chronic HP: Can mimic fibrotic NSIP or even UIP.

    • Fibrosis: Reticulations, traction bronchiectasis, and occasionally honeycombing.

    • Three-Density Pattern: A mosaic attenuation pattern with areas of normal lung, ground-glass opacities, and low attenuation areas (air trapping). This is highly suggestive of HP.

    • Bridging Fibrosis: Fibrosis that extends from the pleura towards the hilum, often with a peribronchovascular distribution.

  • Distribution: Often upper and mid-lung predominance, or diffuse. Spares the lung bases more than IPF.

• Sarcoidosis Pattern: Characterized by granulomatous inflammation.

  • Key Features:
    • Nodules: Perilymphatic distribution of small nodules along bronchovascular bundles, subpleural regions, and fissures. Often clustered or coalescing.

    • Lymphadenopathy: Hilar and mediastinal lymphadenopathy is very common, often bilateral and symmetrical.

    • Reticulations and GGOs: Can be present in advanced fibrotic sarcoidosis.

    • Architectural Distortion: In chronic fibrotic sarcoidosis, often with upper lobe volume loss and traction bronchiectasis.

  • Distribution: Typically upper and mid-lung predominance.

• Asbestosis Pattern: Related to asbestos exposure.

  • Key Features:
    • Pleural Plaques: Calcified or non-calcified pleural thickening, usually bilateral and posterolateral, often sparing the costophrenic angles. Highly characteristic of asbestos exposure.

    • Subpleural Reticulations and Honeycombing: Predominantly in the lower lobes, often mimicking UIP.

    • Parenchymal Bands: Linear opacities extending from the pleura.

  • Distribution: Basal and subpleural predominance.

• Other Patterns:

  • Organizing Pneumonia (OP): Patchy peripheral or peribronchial consolidations, often migratory, with ground-glass opacities. The “atoll sign” or “reverse halo sign” (central ground-glass opacity surrounded by a ring of consolidation) is highly suggestive.

  • Desquamative Interstitial Pneumonia (DIP): Diffuse, usually symmetric ground-glass opacities, sometimes with lower lobe predominance. Often seen in smokers.

  • Lymphocytic Interstitial Pneumonia (LIP): Diffuse ground-glass opacities, centrilobular nodules, and thin-walled cysts. Often associated with Sjögren’s syndrome or HIV.

The Role of Multidisciplinary Discussion (MDD)

Even with characteristic HRCT patterns, the final diagnosis of ILD often requires a multidisciplinary discussion (MDD) involving pulmonologists, radiologists, and pathologists. This collaborative approach ensures that all clinical, radiological, and pathological data are integrated to arrive at the most accurate diagnosis. For instance, an HRCT showing a “probable UIP” pattern in a patient with no history of rheumatological disease might lead to a confident diagnosis of IPF without biopsy, whereas the same pattern in a patient with joint pain and Raynaud’s phenomenon would prompt further investigation for CTD-ILD.

Quantifying Lung Damage: Pulmonary Function Tests (PFTs)

Pulmonary function tests (PFTs) provide objective measurements of lung volumes, airflow, and gas exchange. While not diagnostic of a specific ILD type, they are crucial for assessing the severity of lung impairment, monitoring disease progression, and guiding management.

Key PFT Parameters in ILD

• Spirometry:
  • Forced Vital Capacity (FVC): The total amount of air a person can exhale with force after a deep breath. In ILD, FVC is typically reduced due to the restrictive nature of the disease (fibrosis stiffens the lungs, making them less compliant). A progressive decline in FVC over time is a key indicator of disease progression, particularly in IPF.

  • Forced Expiratory Volume in 1 Second (FEV1): The amount of air exhaled during the first second of a forced breath. In ILD, FEV1 is also reduced, but usually in proportion to FVC, maintaining a normal or elevated FEV1/FVC ratio (>0.7). An obstructive pattern (reduced FEV1/FVC ratio) can suggest co-existing airway disease (e.g., emphysema in combined pulmonary fibrosis and emphysema, or airways involvement in sarcoidosis or chronic HP).

• Lung Volumes:

  • Total Lung Capacity (TLC): The total volume of air the lungs can hold. TLC is characteristically reduced in ILD, confirming a restrictive ventilatory defect. A reduction below 80% of predicted values is typical.

  • Residual Volume (RV): The volume of air remaining in the lungs after a maximal exhalation. RV is also often reduced in ILD.

• Diffusion Capacity of the Lungs for Carbon Monoxide (DLCO): This is arguably the most sensitive PFT parameter for detecting and assessing the severity of ILD.

  • Reduced DLCO: Impaired gas exchange due to thickening and destruction of the alveolar-capillary membrane, which is the hallmark of ILD. A significantly reduced DLCO (e.g., <50% of predicted) indicates substantial gas exchange impairment and is often seen even in early ILD when other PFTs might be near normal.

  • Correlation with Severity: DLCO typically correlates well with the extent of fibrosis on HRCT and is a strong predictor of prognosis in many ILDs.

• 6-Minute Walk Test (6MWT): While not a PFT in the traditional sense, the 6MWT assesses functional capacity and is an important part of the ILD workup.

  • Distance Walked and Oxygen Desaturation: Patients with ILD often experience significant oxygen desaturation during exertion, even with minimal dyspnea at rest. A decrease in walk distance and an increase in oxygen desaturation during the 6MWT indicate worsening functional status and can help identify patients at higher risk of adverse outcomes.

Seeking Serological Clues: Blood Tests

Serological tests play a crucial role in identifying systemic diseases that can manifest with ILD, particularly connective tissue diseases (CTDs).

Autoantibody Testing

• Antinuclear Antibodies (ANAs): A positive ANA test is common in CTDs. While not specific for any particular CTD, a high titer and a specific pattern (e.g., speckled, nucleolar) can guide further testing.

• Extractable Nuclear Antigens (ENAs): A panel of specific autoantibodies that can help pinpoint the underlying CTD:

  • Anti-Jo-1: Highly specific for anti-synthetase syndrome, a subset of inflammatory myositis often associated with severe ILD.

  • Anti-Scl-70 (Topoisomerase I): Specific for systemic sclerosis, particularly the diffuse cutaneous form, which often involves the lungs.

  • Anti-Ro/SSA and Anti-La/SSB: Associated with Sjögren’s syndrome and systemic lupus erythematosus (SLE).

  • Anti-centromere: Associated with limited cutaneous systemic sclerosis (CREST syndrome).

  • Rheumatoid Factor (RF) and Anti-Citrullinated Protein Antibodies (ACPA): Found in rheumatoid arthritis (RA), which is a common cause of CTD-ILD.

• Creatine Kinase (CK): Elevated CK levels suggest muscle inflammation and can point towards inflammatory myopathies (dermatomyositis/polymyositis).

• Angiotensin-Converting Enzyme (ACE) Levels: Elevated ACE levels are seen in approximately 60-80% of patients with sarcoidosis. However, it’s not specific and can be elevated in other conditions. Its primary role is for monitoring disease activity and response to treatment rather than primary diagnosis.

• C-Reactive Protein (CRP) and Erythrocyte Sedimentation Rate (ESR): Non-specific markers of inflammation that can be elevated in various ILDs, particularly those with an inflammatory component like sarcoidosis or CTD-ILD.

The Importance of Context

Interpreting autoantibody results requires careful clinical correlation. A positive ANA in an asymptomatic individual is often not significant. However, a positive ANA along with symptoms like arthralgia, skin rash, or Raynaud’s phenomenon strongly suggests a CTD-ILD. The presence of specific autoantibodies, like anti-Jo-1, significantly narrows the differential diagnosis.

The Definitive Answer: Lung Biopsy

In cases where the clinical and radiological findings are inconclusive, a lung biopsy (surgical lung biopsy or transbronchial lung cryobiopsy) may be necessary to obtain tissue for histological examination. Pathological findings can provide the definitive diagnosis and are crucial for distinguishing between fibrotic and inflammatory patterns.

Types of Lung Biopsy

• Surgical Lung Biopsy (SLB): Traditionally considered the gold standard, SLB involves obtaining larger tissue samples via thoracotomy or video-assisted thoracoscopic surgery (VATS).
  • Advantages: Provides larger, better-preserved tissue samples, allowing for a more confident histological diagnosis, especially for fibrotic ILDs like IPF.

  • Disadvantages: More invasive, associated with higher risks (e.g., pneumothorax, prolonged air leak, even mortality, particularly in frail patients).

• Transbronchial Lung Cryobiopsy (TBLC): A newer, less invasive technique performed during bronchoscopy, where a cryoprobe is used to freeze and retrieve larger tissue samples than conventional forceps biopsies.

  • Advantages: Less invasive than SLB, lower risk profile, good diagnostic yield in experienced centers, especially for non-UIP patterns.

  • Disadvantages: Smaller samples than SLB, may still not be adequate for definitive diagnosis in all cases, especially for subtle UIP patterns. Not universally available.

Histopathological Patterns

The pathologist examines the biopsy tissue for characteristic features that correspond to different ILD types.

• Usual Interstitial Pneumonia (UIP) Pattern:
  • Key Features: Heterogeneity in time (areas of active fibrosis alongside established fibrosis), spatially heterogeneous (patchy involvement), fibroblast foci (clusters of myofibroblasts and collagen), honeycombing, and microscopic areas of normal lung.

  • Significance: This pattern, when seen on biopsy, strongly supports a diagnosis of IPF if other causes are excluded.

• Nonspecific Interstitial Pneumonia (NSIP) Pattern:

  • Key Features: Homogeneous inflammation and/or fibrosis, without the temporal or spatial heterogeneity of UIP. Can be predominantly cellular (inflammation) or fibrotic (collagen deposition).

  • Significance: NSIP is a common pattern in CTD-ILD and drug-induced ILD, but can also be idiopathic.

• Organizing Pneumonia (OP) Pattern:

  • Key Features: Buds of granulation tissue (Masson bodies) filling alveolar spaces and bronchioles, within a background of preserved lung architecture.

  • Significance: OP can be idiopathic (cryptogenic organizing pneumonia, COP) or secondary to infections, drugs, or CTDs. It often responds well to corticosteroids.

• Diffuse Alveolar Damage (DAD) Pattern:

  • Key Features: Acute injury with hyaline membranes, type II pneumocyte hyperplasia, and edema in the acute phase; later organizing phase with fibroblast proliferation and early fibrosis.

  • Significance: DAD is the pathological correlate of acute interstitial pneumonia (AIP) or ARDS.

• Lymphocytic Interstitial Pneumonia (LIP) Pattern:

  • Key Features: Dense interstitial infiltrate of mature lymphocytes, plasma cells, and histiocytes, often forming lymphoid follicles.

  • Significance: Strongly associated with Sjögren’s syndrome, HIV, and other autoimmune conditions.

• Granulomatous Patterns:

  • Non-Caseating Granulomas: Seen in sarcoidosis (often with epithelioid cells and multinucleated giant cells), HP, and berylliosis.

  • Caseating Granulomas: Suggestive of mycobacterial infections or fungal infections.

  • Silicotic Nodules: Well-circumscribed nodules of collagen and dust macropahges with birefringent silica crystals.

When to Biopsy and When to Avoid

The decision to perform a lung biopsy is a complex one, weighing the potential diagnostic benefit against the risks.

• Consider Biopsy When:
  • Clinical and HRCT findings are equivocal or atypical for common ILDs.

  • There’s a suspicion of a treatable ILD (e.g., chronic HP, organizing pneumonia, sarcoidosis) that requires confirmation.

  • Exclusion of malignancy is necessary.

  • The patient’s overall health and comorbidities allow for the procedure.

• Avoid Biopsy When:

  • HRCT shows a definite UIP pattern in the appropriate clinical context (e.g., older patient, no features of CTD), as this is often sufficient for an IPF diagnosis and biopsy carries unnecessary risk.

  • The patient has severe lung impairment or significant comorbidities that make the procedure too risky.

  • The suspected diagnosis is already strongly supported by non-invasive tests and treatment would not change based on biopsy results.

The Holistic Approach: Integrating All Information

Differentiating ILD types is not about relying on a single test result but rather a meticulous integration of all available data points. The process is iterative, with each piece of information refining the diagnostic probability.

• Start Broad, Then Narrow: Initial assessment casts a wide net, considering all potential ILD types. As more information is gathered, the list of possibilities shortens.

• Look for Red Flags and Green Lights:

  • Red Flags for CTD-ILD: Joint pain, skin changes, Raynaud’s, positive autoantibodies.

  • Green Lights for IPF: Older age, male, progressive dyspnea, Velcro crackles, definite UIP on HRCT, no systemic features.

  • Red Flags for HP: Environmental exposures, air trapping on expiratory HRCT, centrilobular nodules.

• The MDD is Key: The multidisciplinary team approach is paramount. Radiologists interpret the images, pulmonologists synthesize clinical data and PFTs, and pathologists analyze tissue. This collective expertise minimizes misdiagnosis and optimizes patient care.

• Consider the Treatable First: Always consider treatable causes of ILD (e.g., chronic HP, drug-induced ILD, sarcoidosis, organizing pneumonia) before landing on idiopathic fibrotic ILDs like IPF, which have limited treatment options.

• Serial Monitoring: ILD is often a progressive disease. Regular follow-up, including PFTs and potentially HRCT, is crucial to monitor disease activity, assess treatment response, and detect complications like pulmonary hypertension.

Concrete Examples in Differentiating ILD Types

Let’s illustrate the diagnostic process with a few hypothetical patient scenarios:

Scenario 1: The “Typical” IPF Presentation

• Patient: 68-year-old male, non-smoker, presenting with 1.5 years of progressive dyspnea on exertion and dry cough. Denies any joint pain, skin changes, or environmental exposures.

• Physical Exam: Bilateral inspiratory Velcro crackles at the lung bases, digital clubbing.

• PFTs: FVC 60% predicted, FEV1/FVC 0.85, TLC 65% predicted, DLCO 35% predicted. (Restrictive ventilatory defect with severe gas exchange impairment).

• Serology: ANA negative, ENA panel negative.

• HRCT: Subpleural and basal predominant reticulations, traction bronchiectasis, and clear honeycombing. No significant ground-glass opacities, nodules, or lymphadenopathy.

• MDD Consensus: Definite UIP pattern on HRCT in the appropriate clinical context, absence of features suggesting other ILDs.

• Diagnosis: Idiopathic Pulmonary Fibrosis (IPF). (No biopsy needed given confident HRCT and clinical picture).

Scenario 2: Suspected Chronic Hypersensitivity Pneumonitis

• Patient: 55-year-old female, non-smoker, presenting with 3 years of gradually worsening dyspnea, cough, and fatigue. Reports keeping pet birds for 10 years. No other systemic symptoms.

• Physical Exam: Bilateral fine inspiratory crackles, less prominent than “Velcro” crackles. No clubbing.

• PFTs: FVC 70% predicted, FEV1/FVC 0.78, TLC 75% predicted, DLCO 45% predicted.

• Serology: ANA negative. Specific precipitins to bird antigens are positive.

• HRCT: Patchy ground-glass opacities, centrilobular nodules, and areas of air-trapping on expiratory scans, predominantly in the mid and upper lobes. Some reticulations and mild traction bronchiectasis, but no honeycombing.

• MDD Consensus: HRCT features highly suggestive of chronic HP, strong occupational exposure history, positive bird precipitins.

• Diagnosis: Chronic Hypersensitivity Pneumonitis (due to bird antigen exposure). (Biopsy might be considered if diagnosis was less clear, but often not necessary with strong clinical-radiological correlation).

Scenario 3: Connective Tissue Disease-Associated ILD (Rheumatoid Arthritis)

• Patient: 48-year-old male, long history of rheumatoid arthritis (on methotrexate for years), now presenting with progressive dyspnea and dry cough over 6 months. Active joint inflammation.

• Physical Exam: Swollen, tender joints in hands and feet. Fine inspiratory crackles at lung bases. No clubbing.

• PFTs: FVC 68% predicted, FEV1/FVC 0.80, TLC 72% predicted, DLCO 40% predicted.

• Serology: RF and ACPA positive (known RA), ANA negative.

• HRCT: Subpleural reticulations and ground-glass opacities, predominantly basal, some areas with mild traction bronchiectasis. No honeycombing. Pattern is consistent with NSIP.

• MDD Consensus: Known rheumatoid arthritis with active disease. HRCT pattern consistent with NSIP, a common manifestation of RA-ILD. Methotrexate also a consideration for drug-induced ILD, but the NSIP pattern is also consistent with RA.

• Diagnosis: Rheumatoid Arthritis-Associated Interstitial Lung Disease (RA-ILD) with an NSIP pattern. (Discontinuation of methotrexate and assessing clinical response would be part of management).

Scenario 4: Sarcoidosis

• Patient: 32-year-old female, presenting with persistent dry cough, fatigue, and bilateral ankle pain for 3 months. Noticed some painful reddish lumps on her shins.

• Physical Exam: Erythema nodosum on shins, bilateral hilar adenopathy on chest X-ray performed by her primary care physician. Crackles are absent.

• PFTs: FVC 85% predicted, FEV1/FVC 0.82, TLC 90% predicted, DLCO 70% predicted. (Often less severe restriction in early sarcoidosis).

• Serology: ACE level elevated. ANA negative.

• HRCT: Bilateral symmetrical hilar and mediastinal lymphadenopathy. Perilymphatic nodules along bronchovascular bundles and pleural surfaces, predominantly in the upper and mid-lungs. No honeycombing.

• Bronchoscopy with Biopsy: Transbronchial biopsy revealed non-caseating granulomas.

• MDD Consensus: Classic clinical presentation (Löfgren’s syndrome variant), characteristic HRCT, and confirmatory biopsy showing non-caseating granulomas.

• Diagnosis: Sarcoidosis.

Conclusion

Differentiating interstitial lung disease types is a challenging but critical endeavor in respiratory medicine. It demands a meticulous, integrated approach, combining a detailed clinical history, comprehensive physical examination, advanced imaging with HRCT, objective pulmonary function tests, targeted serological markers, and, when necessary, lung biopsy. Each piece of the puzzle contributes to building a complete diagnostic picture. The multidisciplinary discussion, bringing together the expertise of pulmonologists, radiologists, and pathologists, is the cornerstone of accurate diagnosis, ensuring that patients receive the most appropriate and timely management. By adhering to this systematic framework, healthcare professionals can navigate the complexities of ILD, ultimately leading to improved patient outcomes and a better understanding of these intricate lung diseases.