Pulmonary Alveolar Proteinosis Associated with Fanconi’s Anemia

Eldar, M; Shoenfeld, Y.; Zaizov, Rina; Fogel, Robert; Asherov, J; Liban, E; Pinkhas, J

doi:10.1159/000194077

Cited by 18 publications

(3 citation statements)

References 5 publications

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“…The diagnosis is usually made based on the presence of typical radiological manifestations and lung histopathological findings. Secondary PAP has been reported in association with various diverse clinical disorders, including hematological disorders (myelodysplastic syndrome, leukemia, lymphoma, aplastic anemia, pharmacologically induced leukopenia, others), immunological diseases (severe combined immunodeficiency, monoclonal gammopathy, selective immunoglobulin A deficiency, others), lysinuric protein intolerance, and infections (Cytomegalovirus, Mycobacterium tuberculosis , Nocardia, Pneumocystis jiroveci , others) [34; 62; 63; 64; 65; 66; 67; 68; 69; 70; 71; 72; 73; 74; 75; 76; 77; 78; 79; 80]. It has also been reported in association with various toxic inhalation syndromes, including inhalation of inorganic dusts (silica, cement, titanium, and aluminum), organic dusts (sawdust, fertilizer, bakery flour, others), and fumes (chlorine, varnish, others) [81; 82; 83; 84; 85; 86; 87; 88].…”

Section: Pathogenesis Of Secondary Papmentioning

confidence: 99%

The molecular basis of pulmonary alveolar proteinosis

Carey¹,

Trapnell²

2010

Clinical Immunology

209

190

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Pulmonary alveolar proteinosis (PAP) comprises a heterogenous group of diseases characterized by abnormal surfactant accumulation resulting in respiratory insufficiency, and defects in alveolar macrophage-and neutrophil-mediated host defense. Basic, clinical and translational research over the past two decades have raised PAP from obscurity, identifying the molecular pathogenesis in over 90% of cases as a spectrum of diseases involving the disruption of GM-CSF signaling. Autoimmune PAP represents the vast majority of cases and is caused by neutralizing GM-CSF autoantibodies. Genetic mutations that disrupt GM-CSF receptor signaling comprise a rare form of hereditary PAP. In both autoimmune and hereditary PAP, loss of GM-CSF signaling blocks the terminal differentiation of alveolar macrophages in the lungs impairing the ability of alveolar macrophages to catabolize surfactant and to perform many host defense functions. Secondary PAP occurs in a variety of clinical diseases that presumedly cause the syndrome by reducing the numbers or functions of alveolar macrophages, thereby impairing alveolar macrophage-mediated pulmonary surfactant clearance. A similar phenotype occurs in mice deficient in the production of GM-CSF or GM-CSF receptors. PAP and related research has uncovered a critical and emerging role for GM-CSF in the regulation of pulmonary surfactant homeostasis, lung host defense, and systemic immunity.

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Section: Pathogenesis Of Secondary Papmentioning

confidence: 99%

The molecular basis of pulmonary alveolar proteinosis

Carey¹,

Trapnell²

2010

Clinical Immunology

209

190

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“…Pulmonary alveolar proteinosis has been described in association with immunodeficiency states154 155 and haematological malignancies 124. It is more common in myeloid leukaemias156-161 but has also been reported in lymphomas,124 Fanconi's anaemia,162 163 and IgG monoclonal gammopathy 164. The overall incidence of secondary pulmonary alveolar proteinosis in patients with haematological malignancies is 5.3%, though it is higher in neutropenic patients (8.8%) and in those with acute myeloid leukaemia (10%) 165.…”

Section: Pathogenesismentioning

confidence: 99%

Rare diseases bullet 6: Pulmonary alveolar proteinosis: clinical aspects and current concepts on pathogenesis

Shah

Hansell²,

Lawson³

et al. 2000

Thorax

238

277

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“…Pulmonary fibrosis was not reported in any of these patients. Rather, pulmonary alveolar proteinosis is the only reported lung complication [Eldar et al, 1979;Steens et al, 1992]. Although pulmonary alveolar proteinosis and ILD are distinct pathologic conditions, a common thread may be that tumor necrosis factor-alpha (TNF␣) is produced by activated macrophages, is induced by mild oxidant stress, and in turn amplifies the production of reactive oxygen species [Pogrebniak et al, 1990].…”

Section: Fa and Ildmentioning

confidence: 99%

Interstitial lung disease in an adult with Fanconi anemia: Clues to the pathogenesis

et al. 1997

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We have studied a 38-year-old man with a prior diagnosis of Holt-Oram syndrome, who presented with diabetes mellitus. He had recently taken prednisone for idiopathic interstitial lung disease and trimethoprim-sulfamethoxazole for sinusitis. Thrombocytopenia progressed to pancytopenia. The patient had skeletal, cardiac, renal, cutaneous, endocrine, hepatic, neurologic, and hematologic manifestations of Fanconi anemia (FA). Chest radiographs showed increased interstitial markings at age 25, dyspnea began in his late 20s, and he stopped smoking at age 32. At age 38, computerized tomography showed bilateral upper lobe fibrosis, lower lobe honeycombing, and bronchiectasis. Pulmonary function tests, compromised at age 29, showed a moderately severe obstructive and restrictive pattern by age 38. Serum alpha-1 antitrypsin level was 224 (normal 85-213) mg/dL and PI phenotype was M1. Karyotype was 46,XY with a marked increase in chromosome aberrations induced in vitro by diepoxybutane. The early onset and degree of pulmonary disease in this patient cannot be fully explained by environmental or known genetic causes. The International Fanconi Anemia Registry (IFAR) contains no example of a similar pulmonary presentation. Gene-environment (ecogenetic) interactions in FA seem evident in the final phenotype. The pathogenic mechanism of lung involvement in FA may relate to oxidative injury and cytokine anomalies.

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Pulmonary Alveolar Proteinosis Associated with Fanconi’s Anemia

Cited by 18 publications

References 5 publications

The molecular basis of pulmonary alveolar proteinosis

The molecular basis of pulmonary alveolar proteinosis

Rare diseases bullet 6: Pulmonary alveolar proteinosis: clinical aspects and current concepts on pathogenesis

Interstitial lung disease in an adult with Fanconi anemia: Clues to the pathogenesis

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