Step 2 CK · Internal Medicine · Pulmonology

Interstitial Lung Disease & Sarcoidosis

Name: Interstitial Lung Disease & Sarcoidosis
Creator: Veli Bakalov, MD

Reading HRCT patterns, spotting exposures, and cracking sarcoidosis

Pulmonology·Interstitial & Diffuse Lung Disease·5 min read·9 high-yield points·Reviewed by Veli Bakalov, MD @HemeOncBuddy

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ILD is restrictive: low TLC and FVC, a preserved or high FEV1/FVC ratio, and a reduced DLCO, with dry cough, exertional dyspnea, Velcro crackles, and sometimes clubbing.
IPF (older male smoker) shows a UIP pattern on HRCT (subpleural, basal reticulation, traction bronchiectasis, honeycombing); a definite UIP pattern can make the diagnosis without biopsy; median survival 3–5 years.
Treat IPF with pirfenidone or nintedanib (slow FVC decline), oxygen, and transplant; prednisone + azathioprine + N-acetylcysteine increased mortality (PANTHER-IPF).
Systemic sclerosis is the connective tissue disease most associated with ILD (NSIP pattern: ground-glass, no honeycombing), and NSIP responds to immunosuppression far better than UIP.
Asbestos = lower lobes, calcified pleural plaques, ferruginous bodies, bronchogenic carcinoma (more common) and mesothelioma after 20–40 years; silica, coal, and beryllium = upper lobes.
Silicosis (sandblasting, mining) causes eggshell-calcified hilar nodes and impairs macrophages, markedly raising TB risk: screen with PPD or IGRA; coal pneumoconiosis + rheumatoid arthritis = Caplan syndrome.
Hypersensitivity pneumonitis (bird-fancier's, farmer's lung from thermophilic actinomycetes) is treated with antigen avoidance, plus steroids for acute or severe disease.
Sarcoidosis = noncaseating granulomas with bilateral hilar adenopathy (classically a young Black woman); biopsy must exclude TB and fungi; ACE is elevated but nonspecific.
Sarcoid hypercalcemia comes from macrophage 1α-hydroxylase making calcitriol (PTH suppressed); Löfgren syndrome (erythema nodosum + hilar adenopathy + polyarthralgia) remits well, and steroids are reserved for symptomatic or cardiac, neurologic, ocular, or hypercalcemic disease.

Recognizing ILD and building the workup

Clinical picture. Interstitial lung disease (ILD) causes exertional dyspnea and a dry cough. On exam there are fine, "Velcro" inspiratory crackles at the bases, and some patients have clubbing.

Restrictive physiology. Fibrosis makes the lungs small and stiff. FVC and TLC fall, but the FEV1/FVC ratio is preserved or even high, because stiff lungs recoil well and both values fall together. The thickened interstitium impairs gas transfer, so DLCO is reduced.

Restrictive vs obstructive pattern

Measure	Restrictive (ILD)	Obstructive (COPD)
TLC	Low	High (hyperinflation)
FEV1/FVC	Normal or high	<0.7
DLCO	Reduced (impaired diffusion)	Low or normal (airflow is the problem)

Workup.

Take a detailed occupational, exposure, and drug history. Drugs that cause ILD include amiodarone, bleomycin, methotrexate, and nitrofurantoin.
HRCT to identify the pattern
PFTs with DLCO
Serologies for connective tissue disease: ANA, RF, myositis panel
Bronchoscopy with bronchoalveolar lavage (BAL) or biopsy when the diagnosis is still unclear

IPF and connective-tissue-disease ILD

Idiopathic pulmonary fibrosis (IPF). Typically affects older men, often smokers, with progressive dyspnea over months to years. HRCT shows a usual interstitial pneumonia (UIP) pattern: subpleural, basal-predominant reticulation, traction bronchiectasis, and honeycombing. In the right clinical setting, a definite UIP pattern establishes IPF without a surgical lung biopsy. Median survival is only 3–5 years.

Treating IPF. The antifibrotics pirfenidone and nintedanib slow the decline in FVC but do not reverse fibrosis. Give supplemental oxygen for hypoxemia. Lung transplant is the only definitive therapy.

Immunosuppression harms patients with IPF. In the PANTHER-IPF trial, prednisone plus azathioprine plus N-acetylcysteine increased mortality.

Connective-tissue-disease ILD. Systemic sclerosis (scleroderma) is the most common and deadliest association, usually with a nonspecific interstitial pneumonia (NSIP) pattern. Other associations are rheumatoid arthritis, dermatomyositis and antisynthetase syndrome (anti-Jo-1), SLE, and Sjögren syndrome.

UIP vs NSIP

Feature	UIP (IPF pattern)	NSIP
HRCT	Subpleural, basal reticulation; traction bronchiectasis; honeycombing	Uniform ground-glass, often lower lobe; no honeycombing
Typical setting	Idiopathic, older male smoker	Connective tissue disease (especially scleroderma)
Steroids and immunosuppression	Not effective (harmful in IPF)	More responsive
Main therapy	Antifibrotics, oxygen, transplant	Immunosuppression

UIP/IPF is the exception: NSIP and most other ILDs do respond to steroids.

Exposure-related disease: hypersensitivity pneumonitis and pneumoconioses

Hypersensitivity pneumonitis. An immune reaction to inhaled organic antigens. Examples are bird-fancier's lung (avian proteins) and farmer's lung (thermophilic actinomycetes in moldy hay). Acute episodes cause fever, cough, and dyspnea hours after exposure. The chronic form causes upper-lobe fibrosis. Treatment is antigen avoidance, with steroids for acute or severe disease.

Pneumoconioses. Fibrosis from inhaled inorganic dust. Remember the zones: asbestos affects the lower lobes, while silica, coal, and beryllium affect the upper lobes.

Pneumoconioses at a glance

Dust	Exposure	Zone	Hallmarks
Asbestos	Shipbuilding, roofing, insulation, old plumbing	Lower lobes	Calcified pleural plaques; ferruginous bodies; bronchogenic carcinoma (more common) and mesothelioma after a 20–40 year latency
Silica	Sandblasting, mining, quarrying, stone-cutting	Upper lobes	Nodules; eggshell calcification of hilar nodes; high risk of TB and other mycobacteria
Coal dust	Coal mining	Upper lobes	Macules; with rheumatoid arthritis = Caplan syndrome
Beryllium	Aerospace, electronics, nuclear industries	Upper lobes	Noncaseating granulomas that mimic sarcoidosis

Silica and TB. Silica impairs macrophage function, so silicosis markedly increases the risk of tuberculosis and other mycobacterial infections. Screen with a PPD or IGRA.

Asbestos and smoking multiply each other's risk: together they raise bronchogenic carcinoma risk far more than either alone. Bronchogenic carcinoma remains more common than mesothelioma in asbestos-exposed patients.

Sarcoidosis: presentation and diagnosis

The disease. Sarcoidosis is a systemic disease of noncaseating granulomas. The classic patient is a young Black woman with bilateral hilar lymphadenopathy on chest x-ray. The lungs are involved in most patients, and the disease is restrictive when it involves the parenchyma.

Eyes: uveitis
Skin: erythema nodosum; lupus pernio (violaceous plaques on the nose and cheeks)
Nerves: cranial nerve VII (facial) palsy
Heart: conduction block (a cause of sudden death)
Calcium: hypercalcemia, hypercalciuria, kidney stones

Diagnosis. Serum ACE is often elevated but nonspecific, so it neither confirms nor excludes the diagnosis. Biopsy, often by bronchoscopy of hilar nodes, shows noncaseating granulomas. Stains and cultures must exclude TB and fungal infection, which also form granulomas. BAL typically shows lymphocytosis with a high CD4:CD8 ratio.

Scadding stages (chest x-ray). Stage 0 is a normal film. Stage I is hilar adenopathy alone. Stage II is adenopathy plus parenchymal infiltrates. Stage III is infiltrates without adenopathy. Stage IV is fibrosis.

Sarcoidosis: hypercalcemia, Löfgren syndrome, and treatment

Granuloma macrophagesExpress 1α-hydroxylase, without regulation by PTH.
25-OH vitamin D → 1,25-(OH)2 vitamin DActive calcitriol is produced.
Gut calcium absorption risesPTH becomes suppressed.
Hypercalcemia and hypercalciuriaKidney stones.

In sarcoid hypercalcemia, PTH is low. The calcium comes from unregulated calcitriol, not from PTH or PTHrP. Glucocorticoids correct it by suppressing granuloma 1α-hydroxylase.

Löfgren syndrome. An acute presentation of sarcoidosis with a good prognosis and a high rate of spontaneous remission. The triad is erythema nodosum, bilateral hilar adenopathy, and migratory polyarthralgias, often with fever. NSAIDs are frequently the only treatment needed.

Who gets treated. Many cases remit spontaneously, so asymptomatic hilar adenopathy (stage I) is usually just observed. Give systemic corticosteroids for symptomatic or progressive pulmonary disease, or for organ-threatening involvement:

Cardiac
Neurologic
Ocular
Hypercalcemia

Methotrexate is the usual steroid-sparing agent. An elevated ACE level alone is never a reason to treat.