Pulmonary Alveolar Proteinosis Clinical Presentation
- Author: Roger B Olade, MD, MPH; Chief Editor: Zab Mosenifar, MD, FACP, FCCP more...
Patients with pulmonary alveolar proteinosis (PAP) typically present with a gradual onset of symptoms. As many as 30% of patients are asymptomatic, even with diffuse chest radiograph (CXR) abnormalities. Symptoms include the following:
- Persistent dry cough (or scant sputum production)
- Progressive dyspnea
- Fatigue and malaise
- Weight loss
- Intermittent low-grade fever and/or night sweats
- Pleuritic chest pain
- Cyanosis (rare)
- Hemoptysis (rare)
Physical findings are usually nonspecific. Symptoms include the following:
- Fine end-inspiratory crackles
- Clubbing (25%)
- Cyanosis (20%)
- Pulmonary hypertension and cor pulmonale (rare)
The etiology of pulmonary alveolar proteinosis (PAP) is unknown, but it has been associated with a number of other processes, implying a causal relationship. Causes may include the following:
- Inhalation of silica dust (acute silicoproteinosis)
- Exposure to insecticides, aluminum dust, titanium dioxide, indium-tin oxide and other inorganic dusts[5, 6, 7]
- Hematologic malignancies, mostly myeloid disorders
- Lysinuric protein intolerance (rare)
- HIV infection (AIDS)
- Leflunomide - Case report (disease-modifying antirheumatic arthritis therapy)
Recessive CSF2RA mutations may cause a rare, hereditary form of PAP. GM-CSF signaling may be absent or severely reduced, and the GM-CSF receptor alpha chain may be absent or abnormal, paralleling the GM-CSF signaling defects. This is unlike secondary PAP, in which a deficiency of GM-CSF and increased autoantibodies are noted. Genetic analysis may reveal multiple distinct CSF2RA abnormalities, including missense, duplication, frameshift, and nonsense mutations; exon and gene deletion; and cryptic alternative splicing.[9, 10]
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