Eosinophilic, Hemorrhagic & Cystic Lung Diseases
Eosinophils, blood, surfactant, and cysts: the lung's specialty diagnoses
Eosinophilic lung diseases
Allergic bronchopulmonary aspergillosis. In asthma or cystic fibrosis, Aspergillus fumigatus colonizes thick airway mucus without invading tissue. The immune response to it, IgE-mediated (type I) plus IgG immune-complex (type III), inflames and dilates the proximal airways. Patients have worsening wheeze, brown mucus plugs, blood eosinophilia, a very high total IgE, Aspergillus-specific IgE and IgG, a positive skin test, fleeting infiltrates and central bronchiectasis. Oral glucocorticoids suppress the reaction, and itraconazole (or voriconazole) reduces the fungal burden and spares steroids. Total IgE tracks activity, and repeated untreated flares lead to fibrotic bronchiectasis. Invasive aspergillosis is the opposite problem: in neutropenia, transplantation or high-dose steroid therapy, hyphae invade vessels, producing nodules with a halo sign, infarction and hemoptysis, and voriconazole is needed.
Löffler syndrome. Larvae of Ascaris, hookworms (Necator, Ancylostoma) and Strongyloides travel through the bloodstream to the lungs, break into alveoli, climb the airways and are swallowed. Their passage causes transient, migratory infiltrates with blood eosinophilia and mild cough or wheeze that clear within weeks. Stool ova may be absent at this stage because eggs appear only after the worms mature in the gut.
Screen for or empirically treat Strongyloides before high-dose glucocorticoids in at-risk patients: steroids can trigger hyperinfection with disseminated larvae and gram-negative sepsis.
| Disease | Setting | Tempo and findings | Course |
|---|---|---|---|
| Acute eosinophilic pneumonia | Young adults days to weeks after starting or resuming smoking, vaping; daptomycin | Fever and rapid hypoxemic failure mimicking ARDS; BAL eosinophils >25%; blood eosinophils often normal early | Rapid, lasting response to steroids; rarely relapses |
| Chronic eosinophilic pneumonia | Middle-aged women, often with asthma; usually nonsmokers | Weeks to months of cough, fever, night sweats, weight loss; blood eosinophilia, often raised IgE; peripheral upper-zone infiltrates | Fast steroid response; relapses on tapering |
| Löffler syndrome | Larval migration (Ascaris, hookworm, Strongyloides) | Migratory infiltrates, eosinophilia, mild symptoms | Self-limited; treat the parasite |
| Drug-induced | Nitrofurantoin, daptomycin | Fever, dyspnea, infiltrates, eosinophilia within days to weeks | Resolves when the drug is stopped |
The photographic negative. Cardiogenic pulmonary edema fills the central, perihilar lung in a bat-wing pattern. Chronic eosinophilic pneumonia does the reverse, with dense peripheral, subpleural infiltrates, mainly in the upper zones, that spare the hila.
Diffuse alveolar hemorrhage
Presentation. Injury to the alveolar capillaries, usually capillaritis, floods the air spaces with blood. Hemoptysis is common but can be absent. Other clues are a falling hematocrit, diffuse infiltrates and hypoxemia. On bronchoalveolar lavage, sequential aliquots grow bloodier, and within days macrophages that have ingested red cells hold Prussian blue–positive hemosiderin.
| Disease | Mechanism | Key markers | Kidney |
|---|---|---|---|
| Anti-GBM disease | Type II hypersensitivity to the α3 chain of type IV collagen | Anti-GBM antibodies; linear IgG on immunofluorescence | Crescentic, rapidly progressive glomerulonephritis |
| Granulomatosis with polyangiitis | Pauci-immune necrotizing vasculitis with granulomas | PR3-ANCA (c-ANCA); sinus and nasal disease | Pauci-immune crescentic glomerulonephritis |
| Microscopic polyangiitis | Pauci-immune vasculitis without granulomas | MPO-ANCA (p-ANCA) | Pauci-immune crescentic glomerulonephritis |
| Systemic lupus erythematosus | Immune-complex capillaritis | ANA, anti-dsDNA, low complement | Lupus nephritis, granular deposits |
Anti-GBM disease. The target antigen lies in both glomerular and alveolar basement membranes, but alveolar epitopes are normally hidden; smoking or inhaled toxins expose them, which is why lung bleeding is more common in smokers. Treatment removes and suppresses the antibody with plasmapheresis, glucocorticoids and cyclophosphamide. Nonimmune causes of alveolar bleeding include mitral stenosis, coagulopathy and cocaine. Hemosiderin-laden macrophages that accumulate with chronic congestion from mitral stenosis or left heart failure are called heart failure cells.
Pulmonary alveolar proteinosis
Mechanism. Alveolar macrophages need GM-CSF signaling to mature and break down surfactant. In autoimmune PAP, by far the most common form, autoantibodies neutralize GM-CSF, so surfactant lipids and proteins pile up and fill the alveoli with granular, PAS-positive material while alveolar walls stay thin and uninflamed. Rarer secondary forms follow heavy silica exposure or hematologic cancers.
Findings and treatment. Dyspnea and cough develop insidiously. CT shows crazy-paving (ground glass with superimposed septal thickening), and lavage returns milky, opaque fluid. Crippled macrophages predispose to Nocardia, mycobacterial and fungal infections. Whole-lung lavage is the mainstay, and inhaled GM-CSF is an alternative.
Cystic lung diseases: PLCH and LAM
| Feature | Pulmonary Langerhans cell histiocytosis | Lymphangioleiomyomatosis |
|---|---|---|
| Patient | Young adult smokers, either sex | Women of reproductive age; sporadic or with tuberous sclerosis |
| Lesional cell | Clonal Langerhans cells: CD1a, S-100, langerin; Birbeck granules | Smooth muscle–like LAM cells: HMB-45, smooth muscle actin, estrogen receptors |
| Imaging | Upper- and mid-zone nodules that cavitate into bizarre, thick-walled cysts; costophrenic angles spared | Diffuse, uniform, thin-walled round cysts throughout both lungs |
| Complications | Pneumothorax; diabetes insipidus and lytic bone lesions if multisystem | Recurrent pneumothorax, chylothorax, renal angiomyolipomas |
| Treatment | Smoking cessation, after which lesions may regress | Sirolimus (mTOR inhibitor) |
Birbeck granules. These rod-shaped cytoplasmic granules, sometimes with a bulbous end that looks like a tennis racket on electron microscopy, identify Langerhans cells, which are dendritic antigen-presenting cells.
LAM and mTOR. TSC2 (tuberin) and TSC1 (hamartin) form a complex that switches off the small GTPase Rheb. When either gene is lost, Rheb stays active and mTORC1 drives LAM-cell growth. LAM cells infiltrate airways, vessels and lymphatics; narrowed airways and matrix-degrading proteases create cysts, and blocked lymphatics leak chyle. Serum VEGF-D is elevated and supports the diagnosis. Sirolimus inhibits mTOR and stabilizes lung function. Estrogen appears to promote the disease.
Drug-induced pulmonary fibrosis
- Bleomycin: free-radical DNA damage; lung and skin lack bleomycin hydrolase, the enzyme that inactivates the drug. Toxicity is dose-related and worsened by high inspired oxygen, so later anesthetics use the lowest FiO2 that keeps saturation adequate.
- Busulfan: interstitial fibrosis, along with skin hyperpigmentation.
- Amiodarone: iodine-rich and lipophilic; causes phospholipidosis with foamy macrophages, pneumonitis and fibrosis, plus thyroid dysfunction, hepatotoxicity, corneal deposits and blue-gray skin.
- Methotrexate: subacute hypersensitivity pneumonitis–like reaction that can progress to fibrosis.
- Nitrofurantoin: acute hypersensitivity reaction within days to weeks; long-term prophylaxis, typically in older women, causes chronic interstitial fibrosis.
All produce a restrictive pattern with a low DLCO; stopping the drug early is the key intervention.