Pulmonary Alveolar Proteinosis in Association with Secondary Hemophagocytic Lymphohistiocytosis

Lin, Ji; De, Aliva; Figueiredo, Lisa; Maxwell, Rochelle R.; Wasserman, Emily; Adams, K. R.; Weingarten, Jacqueline; Peek, Giles J.; Miksa, Michael

doi:10.1016/j.jpeds.2016.12.037

Cited by 3 publications

(1 citation statement)

References 27 publications

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“…This underscores the need to make PAP of unknown cause a trigger for immunological review. Congenital immunodeficiencies include agammaglobulinaemia [ 52 ], severe combined immunodeficiency secondary to adenosine deaminase deficiency [ 53 ], secondary haemophagocytic lymphohistiocytosis [ 54 ], infantile hypogammaglobulinaemia with heterozygous OAS1 mutations [ 55 ], hyper-IgM syndrome [ 56 , 57 ], and sporadic and autosomal dominant monocytopenia [ 58 ]. Bone marrow or stem cell transplant may be curative for some immunodeficiencies and specialist advice should always be sought [ 41 ].…”

Section: Aetiologymentioning

confidence: 99%

Pulmonary alveolar proteinosis in children

Bush

Pabary

2020

Breathe

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Pulmonary alveolar proteinosis (PAP) is an umbrella term for a wide spectrum of conditions that have a very characteristic appearance on computed tomography. There is outlining of the secondary pulmonary lobules on the background of ground-glass shadowing and pathologically, filling of the alveolar spaces with normal or abnormal surfactant. PAP is rare and the common causes in children are very different from those seen in adults; autoimmune PAP is rare and macrophage blockade not described in children. There are many genetic causes of PAP, the best known of which are mutations in the genes encoding surfactant protein (SP)-B, SP-C, thyroid transcription factor 1, ATP-binding cassette protein 3, and the granulocyte–macrophage colony-stimulating factor (GM-CSF) receptor α- and β- chains. PAP may also be a manifestation of rheumatological and metabolic disease, congenital immunodeficiency, and haematological malignancy. Precise diagnosis of the underlying cause is essential in planning treatment, as well as for genetic counselling. The evidence base for treatment is poor. Some forms of PAP respond well to whole-lung lavage, and autoimmune PAP, which is much commoner in adults, responds to inhaled or subcutaneous GM-CSF. Emerging therapies based on studies in murine models of PAP include stem-cell transplantation for GM-CSF receptor mutations.Educational aimsTo understand when to suspect that a child has pulmonary alveolar proteinosis (PAP) and how to confirm that this is the cause of the presentation.To show that PAP is an umbrella term for conditions characterised by alveolar filling by normal or abnormal surfactant, and that this term is the start, not the end, of the diagnostic journey.To review the developmental differences in the spectrum of conditions that may cause PAP, and specifically to understand the differences between causes in adults and children.To discuss when to treat PAP with whole-lung lavage and/or granulocyte–macrophage colony-stimulating factor, and review potential promising new therapies.

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Section: Aetiologymentioning

confidence: 99%

Pulmonary alveolar proteinosis in children

Bush

Pabary

2020

Breathe

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Pulmonary Alveolar Proteinosis in Hereditary and Autoimmune Forms With 2 Cases

et al. 2018

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Pulmonary alveolar proteinosis (PAP) is a respiratory pathology characterized by the accumulation and increase of surfactant-derived material in the lungs. In clinical practice, PAP may present as the primary form, which includes autoimmune and hereditary PAP, or as the secondary form. Diffuse alveolar radiopacities on chest x-ray and the crazy-paving pattern on high-resolution computed tomography are important, although not specific findings for PAP. Bronchoalveolar lavage biopsy is a diagnostic method, and whole-lung lavage remains the criterion standard for the treatment of PAP. Evidence is required regarding treatment with exogenous anti–granulocyte/macrophage colony-stimulating factor. Here, we present a 13-year-old male patient with hereditary PAP and a 15-year-old female patient with autoimmune PAP who presented with complaints of easy fatigability and weakness to emphasize the importance of keeping in mind PAP as a differential diagnosis in patients with respiratory failure findings.

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