Diagnosing alveolar pulmonary proteinosis. A, A chest radiograph shows bilateral, often symmetrical alveolar opacities. If a radiograph appears less dense than what is shown here, a “butterfly” appearance may be recognized. B, A crazy paving pattern from ground-glass opacification and overlaid reticulonodular pattern is shown. C, Foamy macrophage from BAL filled with lipid material (May-Grünwad staining) is seen. D, Periodic acid–Schiff (PAS) staining–positive noncellular globules. A large amount of cell debris is characteristic of PAP lavage. E, Histology from a patient with PAP caused by a homozygous GM-CSF-Ra mutation is shown. Note the alveolar filling and normal alveolar walls (haematoxylin-eosin staining). F, The same biopsy with a PAS stain shows amorphous PAS-positive material with abundant oval bodies.
Schematic of age dependency of the manifestation of various alveolar pulmonary proteinosis forms and qualitative estimates of age at clinical manifestation in the major groups of PAP. Note the size of the graphs does not represent their absolute frequency. Autoimmune PAP represents ∼90% of all cases if age of manifestation is not considered.
Analytical results of WLL effluents in patients with different molecularly defined forms of PAP. A, The total amount of protein removed from the left lung (LL) and right lung (RL) during repetitive WLL. Each dot indicates a single WLL. B, Washout kinetics of protein concentration in lavages from different patients are shown. GM-CSF-Ra #1, n = 26; GM-CSF-Ra #2, n = 28; MDS DiGeorge, n = 9; NPC2, n = 4; SP-C, n = 11. C, WLL protein removed varies with intervals used until next lavage. From day 0 through 180, lavage intervals were 1 to 4 days, then 4 weeks, then 1 to 4 days, etc. Note the low amount of protein removed after a short interval from the previous lavage. From day 180 through 540, lavage intervals were always at least 2 weeks and usually 3 to 4 weeks. D, Over-time variation of volume necessary until clear effluent is shown. E, Over-time variation of protein washed out is shown. The detailed descriptions of the PAP cases used here can be found for GM-CSF-Ra -1 in Griese et al,27 for GM-CSF-Ra -2 in Hildebrandt et al14 (subject I), for NPC2 in Reunert et al80 (subject 1), for SP-C (I73T) in Brasch et al,8 for SP-C (C121F) in van Hoorn et al,81 and for MDS DiGeorge2 in Griese et al49 (subject 7). Ethics approval is documented in the individual studies.
Systemic lupus erythematosus, granulomatosis with polyangiitis, microscopic polyangiitis, membranous nephropathy, dermatomyositis with interstitial lung disease, coincident in many other rheumatologic diseases and interstitial lung diseases, lung transplant