Successful Treatment of Autoimmune Pulmonary Alveolar Proteinosis in a Pediatric Patient

Abstract

Patient: Male, 13Final Diagnosis: Pulmonary alveolar protinosis (autoimmune subtype)Symptoms: Dyspnea • general weakness • subfebrile episodesMedication: VincristineClinical Procedure: Bronchoscopy • bronchoalveolar lavage • CT scan • lung biopsy • GM CSF antibody testing • diagnosis confirmation • therapy with inhaled GM-CSF • bilateral lung transplantation • chemotherapy due to PTLDSpecialty: Pediatrics and NeonatologyObjective:Rare diseaseBackground:Pulmonary alveolar proteinosis (PAP) is a rare condition characterized by the intra-alveolar accumulation of surfactant-derived material, which impairs gas exchange and results in respiratory insufficiency. Two major subtypes of PAP are autoimmune and non-autoimmune PAP. The diagnosis relies on clinical presentation, ground glass opacities on CT scan, bronchoscopy with PAS stain of BAL fluid (BALF), lung biopsy with PAS-positive material in the alveoli, and the presence of anti GM-CSF antibodies in serum or BALF for an autoimmune subtype. The therapeutic approach to pediatric cases varies according to age and the general clinical state of the child; however, whole lung lavage (WLL) and inhaled or subcutaneous GM-CSF are generally first-line therapy.Case Report:We report a unique case of an autoimmune type of PAP in a 12-year-old boy, who underwent successful bilateral lung transplantation after inefficacious treatment with GM-CSF, and who developed post-transplant lymphoproliferative disease (PTLD) and was successfully treated with a chemotherapeutic protocol.Conclusions:Although lung transplantation is a rarely used therapeutic approach for patients with an autoimmune subtype of PAP, in cases of inefficacious treatment with other modalities, lung transplantation should be considered.

Whole lung lavage and GM-CSF use for pulmonary alveolar proteinosis in an infant with lysinuric protein intolerance: a case report

“…The rst successful pediatric treatment using inhaled GM-CSF was reported in a 13-year-old girl with autoimmune PAP, who responded to inhaled GM-CSF (sargramostim) after failing conventional therapy with WLL (19). Subsequently, only a few additional pediatric cases have been published with successful inhaled GM-CSF treatment (20)(21)(22)(23)(24). In agreement with previous observations (18), our ndings also suggest that compared to subcutaneous GM-CSF, inhaled GM-CSF might have been more bene cial in mucus mobilization and had fewer side effects.…”

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.…”

Autoimmune pulmonary alveolar proteinosis in children

“…Whereas in adults autoantibodies against GM-CSF are the principal cause of PAP, in children this cause is rarely identified [ 2 ]. Until now, <10 cases have been published [ 3 – 9 ], whereas a genetically caused interruption of signal transduction of the GM-CSF receptor due to mutations in downstream α- or β-subunit of the receptor has been more frequently described [ 2 ].…”