Pulmonary alveolar proteinosis

Abstract

PAP is an ultra-rare disease in which surfactant components, that impair gas exchange, accumulate in the alveolae. There are three types of PAP. The most frequent form, primary PAP, includes autoimmune PAP which accounts for over 90% of all PAP, defined by the presence of circulating anti-GM-CSF antibodies. Secondary PAP is mainly due to haematological disease, infections or inhaling toxic substances, while genetic PAP affects almost exclusively children. PAP is suspected if investigation for interstitial lung disease reveals a crazy-paving pattern on chest CT-scan, and is confirmed by a milky looking bronchoalveolar lavage that gives a positive periodic acid-Schiff (PAS) reaction indicating extracellular proteinaceous material. PAP is now rarely confirmed by surgical lung biopsy.Whole lung lavage (WLL) is still the first line treatment, with an inhaled GM-CSF as second line treatment. Inhalation has been found to be better than subcutaneous injections. Other treatments, such as rituximab or plasmapheresis, seem to be less efficient or ineffective. The main complications of PAP are due to infections by standard pathogens (Streptococcus, Haemophilus, and Enterobacteria) or opportunistic pathogens like mycobacteria, Nocardia, Actinomyces, Aspergillus or Cryptococcus are. The clinical course of PAP is unpredictable and spontaneous improvement can occur. The 5-year actuarial survival rate is 95%.

Granulocyte Macrophage Colony-Stimulating Factor-Specific Autoantibodies and Cerebral Nocardia With Pulmonary Alveolar Proteinosis

“…Pulmonary alveolar proteinosis is mostly autoimmune (90% of cases), and in such cases, it is characterized by a high level of anti-GM-CSF autoantibodies, whereas hereditary PAP results in mutations in genes encoding the GM-CSF receptor [ 3 ].…”

“…Secondary infection is the most common and threatening complication of PAP, occurring in 5%–13% of cases and accounting for 10%–20% of deaths [ 3 ]. Patients with PAP are known to be more susceptible to bacterial, mycobacterial, and fungal infections such as nocardiosis, mycobacteriosis, aspergillosis, and cryptococcosis [ 3 ].…”

“…Secondary infection is the most common and threatening complication of PAP, occurring in 5%–13% of cases and accounting for 10%–20% of deaths [ 3 ]. Patients with PAP are known to be more susceptible to bacterial, mycobacterial, and fungal infections such as nocardiosis, mycobacteriosis, aspergillosis, and cryptococcosis [ 3 ]. The association between PAP and opportunistic infection has been reported since the first description of the disease in 1958 by Rosen et al [ 4 ], with 2 cases of cryptococcosis and 2 cases of nocardiosis among the 27 patients described.…”

“…We decided to treat the patient with prolonged trimethoprim-sulfamethoxazole as a secondary prophylaxis because we considered the patient immunocompromised. In addition, whereas whole-lung lavage is still the gold standard for autoimmune PAP, subcutaneous and inhaled GM-CSF supplementations were reported to be beneficial [ 3 ]. In prospective studies, daily injection of GM-CSF was effective in 43% to 75% of patients at 1 year and 12 weeks, respectively.…”

“…In addition, inhaled GM-CSF presents several advantages: reduced cost, reduced side effects, and 66% efficiency at 3 years. Two clinical trials evaluating the effect of inhaled GM-CSF on PAP patients are ongoing: IMPALA and PAGE [ 3 ]. More recently, rituximab has been proposed as a therapeutic option for the treatment of autoimmune PAP with controversial results.…”