Pulmonary alveolar proteinosis and Niemann Pick disease type B: An unexpected combination

Abstract

BackgroundPulmonary involvement in Niemann-Pick disease (NPD) is a common finding, especially in type B. It usually manifests with symptoms of restrictive lung disease appearing in adulthood but showing gradual deterioration over time. Treatment options have been dramatically limited, with whole lung lavage offering only temporary improvement. Pulmonary alveolar proteinosis (PAP) has been previously mentioned as part of lung disease in NPD, but only in rare cases of type C2. This is the first study that reports the coexistence of autoimmune PAP with NPD type B.Case presentationAn 8 year old female patient with the diagnosis of NPD type B and a 2-year history of respiratory symptoms, presented with another episode of severe respiratory distress. Chest imaging revealed a “crazy paving pattern”, raising concern for PAP. After admission to the intensive care unit and application of non-invasive positive pressure ventilation, a whole lung lavage was performed with return of a milky-appearing proteinaceous fluid. Her status post-lavage was markedly improved, while genetic testing placed the diagnosis of autoimmune PAP. The patient was initiated on inhaled GM-CSF treatment and shows a beneficial outcome to date.ConclusionsIn spite of the patient’s symptoms being consistent with NPD type of lung involvement, clinical findings raised the suspicion of an underlying disorder, which surprisingly proved to be PAP. The detection of anti-GM-CSF autoantibodies in our patient allowed the initiation of inhaled GM-CSF treatment, which is likely to prove more beneficial in her prognosis than repeated lung lavages.

Chronic lung injury and impaired pulmonary function in a mouse model of acid ceramidase deficiency

“…Lipoproteinosis causes severe lung pathology in several other LSDs, such as Gaucher disease and Niemann-Pick disease types B, C1, and C2 (19,46,(51)(52)(53). Corresponding mouse models have been instrumental in characterizing disease progression (10,12,26).…”

Autoimmune pulmonary alveolar proteinosis successfully treated with lung lavage in an adolescent patient: a case report

“…[ 31 ] 13 F SOB Dry cough Fever Exercise intolerance Fatigue No WLL Improved Chile Sideris et al . [ 30 ] 6 F NR Niemann–Pick disease WLL Inhaled rhGM-CSF Improved USA Trukalj et al . [ 29 ] 10 M Frequent respiratory infections Cough No WLL Inhaled rhGM-CSF Bilateral lung transplantation Improved Croatia Gajewska et al .…”

“…It is important to mention that we are not aware of randomized trials of rhGM-CSF therapy in children or adolescents. Trials of rhGM-CSF excluded this age group; hence, there are limited data on this therapy’s safety and efficacy in the pediatric age group and adolescents [ 26 – 30 , 33 – 35 ].…”

Autoimmune pulmonary alveolar proteinosis in an adolescent successfully treated with inhaled rhGM-CSF (molgramostim)

“…Autoimmune PAP occurs less often in children. No epidemiological data exists and only five case reports are published [ 6 , 7 , [13] , [14] , [15] ]. The treatment approach is the same for children as for adults.…”