Pulmonary Eosinophilia Clinical Presentation

Methodical history taking, to exclude infections, foods, medications, or other precipitants, is important before labeling a pulmonary eosinophilic syndrome as intrinsic or idiopathic. The duration of symptoms and the presence of concomitant medical illnesses, such as collagen vascular disease, may be relevant.

• Query patients about the usage of all medications, including dietary supplements, and illicit drugs.
• Loeffler syndrome is precipitated by food, medications, or infections. It is self-limited (usually < 1 mo duration). Symptoms are mild, and the syndrome is characterized by blood eosinophilia and fleeting pulmonary infiltrates, with or without dyspnea.
• AEP: An acute onset of rapidly progressing dyspnea, often accompanied by abdominal complaints and myalgias, usually occurs within 1 week of presentation. Commonly, recent antecedent outdoor activity with considerable dust exposure has occurred. Marked acute hypoxemia, often progressing to respiratory distress, is typical. AEP is distinguished from CEP by its rapid progression, the presence of fever and severe hypoxemia, and no associated history of hypersensitivity to drugs.
• Obtaining a careful travel history is important for assessing the risk of fungal or parasitic infection. Travel to or from areas endemic for parasites (eg, Asia, Africa, Latin America, South America, southeast region of the United States) is of particular relevance to parasitic infection. Parasitic infections tend to cause fever, weight loss, fatigue, dyspnea, dry cough, wheezing, chest discomfort, and, occasionally, hemoptysis. Relevant historical elements for parasitic infections are provided below.

  • Strongyloidiasis: Patients may report skin contact with sand or soil, abdominal pain or distension, and/or diarrhea, with or without immunocompromise. Marked wheezing and/or respiratory distress may occur.
  • Ascariasis: Mild pulmonary symptoms are accompanied by pruritic dermatitis.
  • Schistosomiasis: Patients may report contact with contaminated water and the presence of skin lesions. Symptoms of early infection are mild, but the manifestations of chronic infection include chronic dyspnea. Other symptoms are bladder and gastrointestinal dysfunction, cirrhosis, and, commonly, pulmonary hypertension.
  • Clonorchis sinensis infection: Patients may relate a history of ingestion of inadequately cooked or pickled fish, abdominal pain, nausea, vomiting, and/or diarrhea.
  • Paragonimiasis: Ingestion of inadequately cooked or pickled crustaceans, abdominal pain, nausea, vomiting, diarrhea, testicular pain, and/or CNS manifestations are reported findings. Patients may develop significant hemoptysis or extensive infiltration.
  • Toxocariasis: Findings include skin or oral contact with soil contaminated by canine feces, contact with puppies, and/or seizures. This condition can lead to significant wheezing and, occasionally, respiratory distress. Patients with toxocariasis may also be asymptomatic.
• Fungal infections associated with pulmonary infiltrates and eosinophilia include Aspergillus infections, Coccidioides immitis infections, and other less common infections.

  • Aspergillus infections: Although Aspergillus species are ubiquitous, ask about contact with soil or contaminated water sources.
  • ABPA: Although technically not an infection because it is the host response to colonization by Aspergillus that is etiologic, it is considered here. Wheezing may be severe, and patients eventually develop prominent central bronchiectasis. The mildest form of ABPA is serologically positive (ABPA-S), the moderate form has central bronchiectasis (ABPA-CB), and the severe form includes both central bronchiectasis and other radiologic features (ABPA-CB-ORF). Early treatment has been suggested to prevent progression to more severe parenchymal disease.^[13]
  • C immitis infection: Inquire about recent travel to the southwestern United States.
  • The clinical course of coccidioidomycosis is highly variable, with more than 60% of patients being asymptomatic, while most of the remainder have mild symptoms.
• For intrinsic syndromes, seek the historical elements described below.

  • CEP: Gradual onset of cough, fever, dyspnea, constitutional symptoms, and weight loss occurs. Wheezing, night sweats, chest pain, and, occasionally, hemoptysis may be reported. Respiratory failure is occasionally reported. Half the patients with CEP have a history of asthma.
  • IHES: Patients may complain of constitutional symptoms, dyspnea, cough, wheezing or angioedema (occasionally), and symptoms related to multiple affected organs, particularly those in the cardiovascular, gastrointestinal, and musculoskeletal systems. Symptoms related to arterial and venous thromboembolic disease may be present (eg, pulmonary emboli, vascular insufficiency, cerebrovascular accident).
  • CSS: Patients often have antecedent rhinitis, sinusitis, and nasal polyps, followed by the development of asthma symptoms. Symptoms related to vasculitis occur years later and include mononeuritis multiplex, abdominal pain, gastrointestinal bleeding, symptoms of heart failure, arthralgias, myalgias, urticaria, purpura, and nodular skin lesions.
  • EG: Approximately one fourth of patients are asymptomatic. Most have a cough, dyspnea, fever, and chest discomfort. Wheezing may be reported. Patients may develop symptoms related to the pneumothorax, bony lesions, and diabetes insipidus. Cigarette smoking is nearly universal in these patients and is considered etiologic. The course of EG is highly variable. Patients at age extremes, those with multiorgan or skin involvement, and those with pneumothoraces tend to have a poor prognosis.

A complete physical examination of these patients is necessary. For this heterogeneous group of diseases, clues to establishing a diagnosis are found in virtually every portion of the examination.

• Skin examination

  • A pruritic rash, which may be raised or serpiginous, is often seen.
  • Medication-related syndromes may result in skin manifestations.
  • Parasitic infection, commonly with Strongyloides, Ascaris, Toxocara, Ancylostoma, Necator, and Trichinella species, may cause skin symptoms.
  • Disseminated coccidioidomycosis is related to patients' skin symptoms.
  • A rash associated with IHES may be due to skin infiltration by eosinophils. Splinter hemorrhages and evidence of vascular occlusion may be seen.
• Head, eyes, ears, nose, and throat examination

  • Evidence of rhinitis/sinusitis may be observed in persons with CSS and CEP.
  • Vascular occlusion may be observed during the eye examinations of patients with IHES.
  • Proptosis may be seen in patients with CSS.
• Chest examination

  • All the syndromes discussed can cause rales and wheezing.
  • Physical signs of cardiac decompensation (eg, valvular insufficiency, S₃, rales, jugular venous distension [JVD], peripheral edema) may be present in patients with IHES and CSS.
  • Patients with chronic schistosomiasis may present with signs of pulmonary hypertension (eg, loud P₂, JVD, peripheral edema, right-sided S₃).
• Abdominal examination

  • Patients with chronic schistosomiasis may present with signs of cirrhosis (eg, distended abdomen, shifting dullness, peripheral edema, telangiectasias, icterus).
  • Nonspecific abdominal tenderness is common in patients with parasitic diseases and intrinsic diseases.
• Neurologic examination

  • Neuropathy may be observed in patients with IHES and CSS.
  • Evidence of CNS deficits due to cerebrovascular accident may be observed in patients with IHES.

• Extrinsic syndromes and the eosinophilic immune response can be triggered by inhaled or ingested substances, including medications, drugs (eg, cocaine), food (eg, contaminated cooking oil), dietary supplements (eg, L-tryptophan), and infections (eg, parasites, fungi, mycobacteria).

  • Medications that have been implicated include the following:
    • Antibiotics (among the most common offending agents)
    • Nonsteroidal anti-inflammatory drugs (among the most common offending agents)
    • Antidepressants
    • Contraceptives
    • Antihypertensives
    • Leukotriene inhibitors^[14]
    • Anticonvulsants
    • L-tryptophan
    • Cocaine
  • Parasitic infections due to nematodes, filariae, and helminths may cause pulmonary infiltrates and eosinophilia. Such infections include strongyloidiasis, ascariasis, paragonimiasis, schistosomiasis, dirofilariasis, ancylostomiasis, trichomoniasis, clonorchiasis, and visceral larva migrans.^[15]
  • Fungal processes, such as ABPA and coccidioidomycosis, may also cause pulmonary eosinophilia. Bronchocentric granulomatosis is most commonly related to Aspergillus infection.
  • Other infections may include tuberculosis and Pneumocystis carinii pneumonia.
• Intrinsic syndromes (ie, CEP, IHES, CSS, EG) are idiopathic.
• Asthma can cause pulmonary eosinophilia.
• Occasionally, eosinophilia and pulmonary infiltrates have been associated with AIDS, bronchiolitis obliterans organizing pneumonia (BOOP), hypersensitivity pneumonitis, idiopathic pulmonary fibrosis, sarcoidosis, Hodgkin disease, rheumatoid lung disease, and other collagen vascular diseases.