Eosinophilic Lung Diseases & Allergic Bronchopulmonary Aspergillosis

Approach to lung infiltrates with eosinophilia

Definition. Eosinophilic lung disease means pulmonary infiltrates accompanied by blood eosinophilia (>500/µL) or by BAL eosinophils above 25%, the threshold that points to eosinophilic pneumonia. Blood counts can be normal early in acute eosinophilic pneumonia or in patients already taking steroids, so BAL is often the decisive test.

Sort by tempo and exposure. Days of illness suggest acute eosinophilic pneumonia; weeks to months suggest chronic eosinophilic pneumonia or ABPA. Then ask about new smoking or vaping, drugs (nitrofurantoin, daptomycin, NSAIDs, minocycline), travel or residence in the tropics, and asthma or CF.

Allergic bronchopulmonary aspergillosis

Mechanism. Aspergillus fumigatus colonizes the airways of patients with asthma or cystic fibrosis and provokes IgE-mediated (type I) and immune-complex (type III) eosinophilic inflammation without tissue invasion. Repeated flares cause mucus impaction, central bronchiectasis and, eventually, fibrosis. The fungus causes different diseases depending on host immunity: hypersensitivity in atopic airways, a fungus ball in an old cavity, and invasive infection in neutropenic patients.

Presentation. Asthma or CF becomes difficult to control, with wheeze, low-grade fever and expectoration of brown or black mucus plugs containing hyphae. Chest films show recurrent fleeting infiltrates. CT shows central (proximal) bronchiectasis, finger-in-glove opacities from mucus-filled bronchi and, in some patients, high-attenuation mucus.

Diagnosis. Screen with an Aspergillus skin test or Aspergillus-specific IgE. The diagnosis requires a predisposing condition (asthma or CF), Aspergillus sensitization and a total IgE above 1000 IU/mL (lowered to 500 IU/mL or more in the 2024 ISHAM revision), supported by at least two of blood eosinophils >500/µL, Aspergillus precipitins or IgG, and compatible imaging. A normal total IgE in a patient not taking steroids essentially excludes active ABPA. Serum galactomannan is a test for invasive aspergillosis, not ABPA.

Treatment. Oral prednisone (about 0.5 mg/kg/day, tapered over roughly 3–5 months) controls acute disease. Itraconazole reduces fungal burden, exacerbations and steroid requirements and is used with steroids or for recurrences; amphotericin and surgery have no role because the disease is not invasive. Total IgE is rechecked every 6–8 weeks: it falls with response, and a sharp rise signals relapse, sometimes before symptoms return. In CF, a new IgE surge with mucoid impaction should prompt ABPA treatment rather than another course of antipseudomonal antibiotics.

Itraconazole strongly inhibits CYP3A4; combined with inhaled budesonide or fluticasone it can cause iatrogenic Cushing syndrome and adrenal suppression.

Acute and chronic eosinophilic pneumonia

Acute eosinophilic pneumonia. A young adult who has recently started or resumed smoking or vaping, or had another heavy inhalational exposure, develops fever, cough, pleuritic pain and dyspnea over days, often progressing to hypoxemic respiratory failure that needs ventilation. CT shows diffuse ground glass, interlobular septal thickening and small bilateral effusions that mimic ARDS or pulmonary edema. Blood eosinophils are often normal at first. BAL eosinophils above 25% with negative cultures establish the diagnosis. Systemic steroids produce improvement within 24–48 hours and are given for about 2–4 weeks; relapse is rare if the trigger is avoided.

Chronic eosinophilic pneumonia. Middle-aged women, often nonsmokers with asthma, develop weeks to months of cough, dyspnea, fever, night sweats and weight loss. Radiographs show bilateral peripheral, upper-zone consolidations, the "photographic negative" of pulmonary edema, which is central. Blood eosinophilia is usually present and BAL eosinophils exceed 25%. Prednisone (about 0.5 mg/kg/day) relieves symptoms within days and clears the film within weeks, with a taper over at least 6 months. About half relapse during tapering or after stopping; relapses respond to steroids again, and some patients need long-term low-dose or inhaled steroids.

Parasitic causes

Loeffler syndrome. Larvae of Ascaris lumbricoides (the most common cause), hookworms or Strongyloides pass through the alveoli on their way to the gut, causing transient, migratory infiltrates with blood eosinophilia and mild cough, wheeze or fever that resolve within about 2 weeks. Stool is often negative during the lung phase because eggs appear weeks later, so stool examination is repeated and the worm is treated (albendazole) once found. Pinworm (Enterobius) has no lung phase.

Strongyloides stercoralis can persist for decades through autoinfection. Glucocorticoids, HTLV-1 infection or transplant immunosuppression trigger hyperinfection: larvae swarm through the gut wall and lungs, carrying enteric bacteria that cause gram-negative bacteremia and meningitis, with high mortality. Anyone with endemic exposure and eosinophilia should have serology or stool testing, or empiric ivermectin, before steroids. Ivermectin, not albendazole, is the drug of choice. Larva currens, a fast-moving serpiginous urticarial track on the buttocks or trunk, is a skin clue.

Tropical pulmonary eosinophilia. An exaggerated immune response to the microfilariae of Wuchereria bancrofti or Brugia malayi, typically in people from South or Southeast Asia, causes nocturnal paroxysmal cough and wheeze that is often mistaken for asthma. Eosinophil counts are usually above 3000/µL, IgE and antifilarial antibodies are very high, the chest film shows diffuse reticulonodular opacities, and microfilariae are not found in blood. Diethylcarbamazine for about 3 weeks is curative; untreated disease can progress to fibrosis, and inhaled asthma therapy merely masks it.

Systemic eosinophilic disorders

EGPA (Churg-Strauss). Adult-onset asthma, eosinophilia above 10%, sinusitis or nasal polyps and migratory infiltrates are joined by small-vessel vasculitis: mononeuritis multiplex (foot or wrist drop), palpable purpura, GI and renal involvement, and eosinophilic myocarditis, the leading cause of death. MPO-ANCA (p-ANCA) is positive in only about 40%. Glucocorticoids are the base of therapy, with cyclophosphamide or rituximab for organ-threatening disease and mepolizumab (anti-IL-5) for relapsing disease. Leukotriene antagonists such as montelukast can unmask EGPA by allowing an oral steroid taper. GPA, by contrast, lacks asthma and eosinophilia and is usually PR3-ANCA positive.

Hypereosinophilic syndrome. HES is eosinophilia of at least 1500/µL that persists and damages organs after secondary causes are excluded. The heart is the key target (endomyocardial fibrosis, mural thrombi with emboli, restrictive cardiomyopathy), along with lung, skin and nerves, so echocardiography is part of the workup.