CASE REPORT
The Clinical Respiratory Journal
Endogenous lipoid pneumonia preceding diagnosis of pulmonary alveolar proteinosis James W. Antoon1, Michelle L. Hernandez2, Phillip A. Roehrs3, Terry L. Noah4, Margaret W. Leigh4 and Julie S. Byerley1 1 Division of General Pediatrics and Adolescent Medicine, UNC Hospitals, University of North Carolina School of Medicine, Chapel Hill, NC, USA 2 Division of Allergy, Immunology, Rheumatology and Infectious Diseases, UNC Hospitals, University of North Carolina School of Medicine, Chapel Hill, NC, USA 3 Division of Hematology and Oncology, UNC Hospitals, University of North Carolina School of Medicine, Chapel Hill, NC, USA 4 Division of Pulmonology, Department of Pediatrics, UNC Hospitals, University of North Carolina School of Medicine, Chapel Hill, NC, USA
Abstract Pulmonary alveolar proteinosis (PAP) is an under-reported and under-diagnosed condition, with a high percentage of cases found on autopsy or late stage disease. The etiology of PAP includes genetic, primary (anti-granulocyte-macrophage colony-stimulating factor antibodies) and secondary (oncologic, rheumatologic, infectious, chemical and immunologic) causes. Here, we present the first reported pediatric case of endogenous lipoid pneumonia and non-specific interstitial pneumonitis preceding the development of PAP. Please cite this paper as: Antoon JW, Hernandez Hernandez ML, ML, Roehrs PA, Noah TL, Leigh MW and preceding diagnosis of pulmoand Byerley ByerleyJS. JS.Endogenous Endogenouslipoid lipoidpneumonia pneumonia preceding diagnosis of pulnary alveolar proteinosis. Clin Clin Respir J 2016; 10: 246–249. monary alveolar proteinosis. Respir J 2014; ••: ••–••. DOI:10.1111/crj.12197. DOI:10.1111/crj.12197.
Key words crazy paving pattern – interstitial lung disease – lipoid pneumonia – non-specific interstitial pneumonitis – pediatric pulmonology – pulmonary alveolar proteinosis Correspondence James W. Antoon, MD, PhD, Division of General Pediatrics and Adolescent Medicine, UNC Hospitals, UNC School of Medicine, 260 MacNider Building CB# 1593, Chapel Hill 27599-7220 North Carolina, USA. Tel: 919 966 3172 Fax: 919 966 8419 email: [email protected] Received: 06 October 2013 Revision requested: 08 February 2014 Accepted: 01 August 2014 DOI:10.1111/crj.12197
Authorship and contributorship James W. Antoon contributed to the initial patient evaluation and treatment plan and drafted the manuscript. Julie S. Byerley contributed to the initial treatment plan and critically reviewed the manuscript. Michelle L. Hernandez consulted on the treatment plan of the patient, critically reviewed the manuscript and contributed to the discussion. Phillip A. Roehrs contributed to the treatment plan of the patient and to the case
presentation and discussion. Margaret W.Leigh consulted on the treatment plan, critically reviewed the manuscript and contributed to the discussion. Terry L. Noah developed the treatment plan and critically reviewed the manuscript. Conflict of interest The authors have stated explicitly that there are no conflicts of interest in connection with this article.
Introduction Pulmonary alveolar proteinosis (PAP) is an underreported and under-diagnosed condition, with a high percentage of cases found on autopsy or late stage
The 246Clinical Respiratory Journal (2014) • ISSN 1752-6981 © 2014 John Wiley & Sons Ltd
Abbreviations: BALF bronchoalveolar lavage fluid DVT deep vein thrombosis ELP endogenous lipoid pneumonia GM-CSF granulocyte-macrophage colonystimulating factor NSIP non-specific interstitial pneumonitis PAP pulmonary alveolar proteinosis
disease. The etiology of PAP includes genetic, primary [anti-granulocyte-macrophage colony-stimulating factor (GM-CSF) antibodies] and secondary (oncologic, rheumatologic, infectious, chemical and immunologic) causes (1). Here, we present the first reported
1 The Clinical Respiratory Journal (2016) • ISSN 1752-6981 C 2014 John Wiley & Sons Ltd V
Antoonpneumonia et al. Lipoid preceding alveolar proteinosis
pediatric case of endogenous lipoid pneumonia (ELP) and non-specific interstitial pneumonitis (NSIP) preceding the development of PAP.
Lipoid pneumonia preceding alveolarAntoon proteinosis et al.
(A)
Case report A 16-year-old Caucasian girl with a history of depression and essential hypertension was admitted to the hospital with persistent cellulitis and methicillinresistant Staphylococcus aureus abscess formation, which was successfully treated with clindamycin and ampicillin/sulbactam. Her hospital course was complicated by deep vein thrombosis (DVT) and acute kidney injury, which was presumed to be drug related. Late in her hospital stay, she developed mild hypoxia, dyspnea and pneumomediastinum of unclear etiology, which spontaneously resolved. Evaluation for pulmonary embolism was negative. She was discharged from the hospital 6 weeks after her initial admission for cellulitis. Outpatient pulmonary function following discharge demonstrated a restrictive pattern with impaired diffusion capacity. One month later, the patient was seen in clinic and complained of mild but persistent pleuritic chest pain. She was discovered to be hypoxic with exertion and was readmitted to the hospital. Associated symptoms included intermittent difficulty sleeping, dry cough and shortness of breath on exertion. She denied recent drug abuse, aspiration or suspicious ingestions. There was exposure to cats and chickens in the past month. Recent medications in addition to the antibiotics had included ferrous sulfate, lisinopril, tramadol, lamictal, warfarin (for her DVT), promethazine and omeprazole. Vital signs, including respiratory rate, were normal. Oxygen saturation was 98% while resting but dropped to 82% on exertion. Physical examination revealed an awake and alert teenager in no acute distress. Lungs were clear bilaterally although deep inspiration was inhibited secondary to chest pain. High resolution computed tomography (CT) scan on admission revealed a pattern of perilobular septal thickening with multifocal ground glass opacities (a ‘crazy paving’ pattern) in both lower lobes, and less extensively in the right middle lobe and lingula (Fig. 1A). Right lower lobe bronchoalveolar lavage fluid (BALF) showed numerous macrophages and positive fat stains in a pattern consistent with endogenous lipid deposition. PAS stain in BALF was negative. Surgical lung biopsy of the left upper lobe revealed hyperinflation, alveolar septal destruction and alveolar accumulation of foamy macrophages consistent with ELP and NSIP (Fig. 2A). There was no evidence of PAP on initial biopsy.
The Clinical Respiratory Journal (2016) • ISSN 1752-6981 2
C 2014 John Wiley & Sons Ltd V
(B)
Figure 1. Lipoid pneumonia with crazy paving pattern. (A) High resolution computed tomography (CT) scan of the chest on the day of admission showing combined pattern of smooth perilobular septal thickening with multifocal ground glass opacities or ‘crazy paving pattern’. (B) Chest CT on hospital day 16 demonstrating worsened appearance of patchy ground glass opacity and intralobular sepal thickening. Scale bar equal to 500 μm.
Over the next 8 weeks, she developed subcutaneous emphysema, continued chest pain, persistent and progressively worsening hypoxia, intermittent mild elevation of transaminases and pancreatic enzymes, pericarditis, pericardial effusions, polyarticular arthralgia and pulmonary hypertension. Her lung function with restrictive pattern continued to worsen and follow-up CT scans revealed wide-spread interstitial patchy ground glass opacity with intralobular sepal thickening involving all lung fields (Fig. 2B). She underwent an exhaustive diagnostic workup to identify the cause of her underlying ELP, including negative workups for surfactant protein gene mutations, Neiman Pick disease, juvenile idiopathic arthritis, 247 The Clinical Respiratory Journal (2014) • ISSN 1752-6981 © 2014 John Wiley & Sons Ltd
Lipoid pneumonia preceding alveolar proteinosis Antoon et al.
(A)
et al. Lipoid pneumonia preceding alveolarAntoon proteinosis
tion was felt to be contraindicated due to the ambiguity of her underlying diagnosis, her markedly elevated body mass index and her inability to wean from high dose corticosteroids and analgesics. She remained as an inpatient dependent on high flow oxygen, bi-level positive airway pressure and analgesics and died 10 months after admission. Autopsy of the lungs showed a definitive diagnosis of PAP (Fig. 2B).
Discussion
(B)
Figure 2. Histopathology of endogenous lipoid pneumonia and pulmonary alveolar proteinosis. (A) Lung biopsy histopathology demonstrating alveolar accumulation of foamy macrophages (arrows) consistent with endogenous lipoid pneumonia. (B) Lung histopathology at autopsy showed diffuse interstitial and alveolar pulmonary disease (with sparing of portion of left lower lobe), with abundant lipoproteinaceous granular debris filling the alveolar spaces. Diagnosis was confirmed using electron microscopy. Scale bar equal to 500 μm.
granulomatosis with polyangiitis and other autoimmune disorders. It was thought that her initial cellulitis was an initiating event for the presentation of an underlying connective tissue disease or immune disorder. Various empiric treatments, including antibiotics, antivirals, antifungals, immunosuppression and plasmapheresis did not elicit a therapeutic response. She partially responded to high dose corticosteroids and cyclophosphamide, but unfortunately, the deterioration in her lung function was not reversible. Repeat lung biopsy or bronchoscopy was not undertaken because of her degree of respiratory compromise. Lung transplanta248Clinical Respiratory Journal (2014) • ISSN 1752-6981 The © 2014 John Wiley & Sons Ltd
We report what we believe to be the first pediatric case of endogenous lipoid pneumonia and NSIP preceding the development of PAP. Initial biopsy specimens were evaluated by pulmonary pathologists from three separate academic institutions, and there was no evidence of PAP at that time. However, autopsy 10 months later revealed extensive PAP, believed to be the primary cause of death. Based on her multitude of systemic symptoms, negative family history of PAP and adolescent age, our patient likely had secondary PAP with an unknown triggering etiology. To the best of our knowledge, there are no reported cases of ELP or NSIP progressing to PAP in the literature. Surfactant protein deficiency can cause both NSIP and PAP, which presents with clinical symptoms early in life (2). There are three published studies of coexisting ELP and PAP . McDonald et al. reported a case of a 5 year old with recurrent aspiration who was found to have PAP and ELP on biopsy (3). Sato et al. reported of a case of an 18 year old with ELP and PAP, with PAP being much less extensive than ELP at time of autopsy (4). Fisher et al. pushed a series of eight patients with ELP and PAP (5). All of these patients had coexisting disease at time of diagnosis, with four patients having primarily ELP and two with moreextensive PAP on initial tissue sampling. Our patient’s disease progression was similar to one patient in the Fisher series, a 3 year old with lysinuric protein intolerance and glucose-6-phosphate dehydrogenase deficiency, who had mostly ELP on initial biopsy with more-extensive PAP on autopsy. However, our patient differed in age, presentation, associated symptoms and did not have signs of PAP on her initial biopsy. It is unclear whether a precipitating factor, such as a bacterial toxin or underlying autoimmune disease, resulted in independent development of ELP and PAP. Whole-lung lavage, which would have been feasible only with extracorporeal membrane oxygenation support, was not considered due to the negative prior workup for PAP. We speculate that ELP may be an early finding in the development of PAP, and we The Clinical Respiratory Journal (2016) • ISSN 1752-6981 3 C 2014 John Wiley & Sons Ltd V
Antoonpneumonia et al. Lipoid preceding alveolar proteinosis
recommend that PAP testing, including serum and BAL anti-GM-CSF antibody, be considered in pediatric patients with ELP or NSIP and subsequent further respiratory deterioration.
Acknowledgments We thank Drs William K. Funkhouser, H. Michael Jones and Nathan D. Montgomery for their help with histopathology.
References 1. Das M, Salzman GA. Pulmonary alveolar proteinosis: an overview for internists and hospital physicians. Hosp Pract (1995). 2010;38(1): 43–9. [Review]. 2. Brasch F, Griese M, Tredano M, et al. Interstitial lung disease in a baby with a de novo mutation in the SFTPC
The Clinical Respiratory Journal (2016) • ISSN 1752-6981 4
C 2014 John Wiley & Sons Ltd V
Lipoid pneumonia preceding alveolarAntoon proteinosis et al.
gene. Eur Respir J. 2004;24(1): 30–9. [Case Reports Comparative Study Research Support, Non-U.S. Gov’t Research Support, U.S. Gov’t, P.H.S. Review]. 3. McDonald JW, Roggli VL, Bradford WD. Coexisting endogenous and exogenous lipoid pneumonia and pulmonary alveolar proteinosis in a patient with neurodevelopmental disease. Pediatr Pathol. 1994;14(3): 505–11. Affiliated with the International Paediatric Pathology Association. [Case Reports]. 4. Sato K, Takahashi H, Amano H, Uekusa T, Dambara T, Kira S. Diffuse progressive pulmonary interstitial and intra-alveolar cholesterol granulomas in childhood. Eur Respir J. 1996;9(11): 2419–22. [Case Reports]. 5. Fisher M, Roggli V, Merten D, Mulvihill D, Spock A. Coexisting endogenous lipoid pneumonia, cholesterol granulomas, and pulmonary alveolar proteinosis in a pediatric population: a clinical, radiographic, and pathologic correlation. Pediatr Pathol. 1992;12(3): 365–83. Affiliated with the International Paediatric Pathology Association. [Case Reports].
249 The Clinical Respiratory Journal (2014) • ISSN 1752-6981 © 2014 John Wiley & Sons Ltd
The Clinical Respiratory Journal
Endogenous lipoid pneumonia preceding diagnosis of pulmonary alveolar proteinosis James W. Antoon1, Michelle L. Hernandez2, Phillip A. Roehrs3, Terry L. Noah4, Margaret W. Leigh4 and Julie S. Byerley1 1 Division of General Pediatrics and Adolescent Medicine, UNC Hospitals, University of North Carolina School of Medicine, Chapel Hill, NC, USA 2 Division of Allergy, Immunology, Rheumatology and Infectious Diseases, UNC Hospitals, University of North Carolina School of Medicine, Chapel Hill, NC, USA 3 Division of Hematology and Oncology, UNC Hospitals, University of North Carolina School of Medicine, Chapel Hill, NC, USA 4 Division of Pulmonology, Department of Pediatrics, UNC Hospitals, University of North Carolina School of Medicine, Chapel Hill, NC, USA
Abstract Pulmonary alveolar proteinosis (PAP) is an under-reported and under-diagnosed condition, with a high percentage of cases found on autopsy or late stage disease. The etiology of PAP includes genetic, primary (anti-granulocyte-macrophage colony-stimulating factor antibodies) and secondary (oncologic, rheumatologic, infectious, chemical and immunologic) causes. Here, we present the first reported pediatric case of endogenous lipoid pneumonia and non-specific interstitial pneumonitis preceding the development of PAP. Please cite this paper as: Antoon JW, Hernandez Hernandez ML, ML, Roehrs PA, Noah TL, Leigh MW and preceding diagnosis of pulmoand Byerley ByerleyJS. JS.Endogenous Endogenouslipoid lipoidpneumonia pneumonia preceding diagnosis of pulnary alveolar proteinosis. Clin Clin Respir J 2016; 10: 246–249. monary alveolar proteinosis. Respir J 2014; ••: ••–••. DOI:10.1111/crj.12197. DOI:10.1111/crj.12197.
Key words crazy paving pattern – interstitial lung disease – lipoid pneumonia – non-specific interstitial pneumonitis – pediatric pulmonology – pulmonary alveolar proteinosis Correspondence James W. Antoon, MD, PhD, Division of General Pediatrics and Adolescent Medicine, UNC Hospitals, UNC School of Medicine, 260 MacNider Building CB# 1593, Chapel Hill 27599-7220 North Carolina, USA. Tel: 919 966 3172 Fax: 919 966 8419 email: [email protected] Received: 06 October 2013 Revision requested: 08 February 2014 Accepted: 01 August 2014 DOI:10.1111/crj.12197
Authorship and contributorship James W. Antoon contributed to the initial patient evaluation and treatment plan and drafted the manuscript. Julie S. Byerley contributed to the initial treatment plan and critically reviewed the manuscript. Michelle L. Hernandez consulted on the treatment plan of the patient, critically reviewed the manuscript and contributed to the discussion. Phillip A. Roehrs contributed to the treatment plan of the patient and to the case
presentation and discussion. Margaret W.Leigh consulted on the treatment plan, critically reviewed the manuscript and contributed to the discussion. Terry L. Noah developed the treatment plan and critically reviewed the manuscript. Conflict of interest The authors have stated explicitly that there are no conflicts of interest in connection with this article.
Introduction Pulmonary alveolar proteinosis (PAP) is an underreported and under-diagnosed condition, with a high percentage of cases found on autopsy or late stage
The 246Clinical Respiratory Journal (2014) • ISSN 1752-6981 © 2014 John Wiley & Sons Ltd
Abbreviations: BALF bronchoalveolar lavage fluid DVT deep vein thrombosis ELP endogenous lipoid pneumonia GM-CSF granulocyte-macrophage colonystimulating factor NSIP non-specific interstitial pneumonitis PAP pulmonary alveolar proteinosis
disease. The etiology of PAP includes genetic, primary [anti-granulocyte-macrophage colony-stimulating factor (GM-CSF) antibodies] and secondary (oncologic, rheumatologic, infectious, chemical and immunologic) causes (1). Here, we present the first reported
1 The Clinical Respiratory Journal (2016) • ISSN 1752-6981 C 2014 John Wiley & Sons Ltd V
Antoonpneumonia et al. Lipoid preceding alveolar proteinosis
pediatric case of endogenous lipoid pneumonia (ELP) and non-specific interstitial pneumonitis (NSIP) preceding the development of PAP.
Lipoid pneumonia preceding alveolarAntoon proteinosis et al.
(A)
Case report A 16-year-old Caucasian girl with a history of depression and essential hypertension was admitted to the hospital with persistent cellulitis and methicillinresistant Staphylococcus aureus abscess formation, which was successfully treated with clindamycin and ampicillin/sulbactam. Her hospital course was complicated by deep vein thrombosis (DVT) and acute kidney injury, which was presumed to be drug related. Late in her hospital stay, she developed mild hypoxia, dyspnea and pneumomediastinum of unclear etiology, which spontaneously resolved. Evaluation for pulmonary embolism was negative. She was discharged from the hospital 6 weeks after her initial admission for cellulitis. Outpatient pulmonary function following discharge demonstrated a restrictive pattern with impaired diffusion capacity. One month later, the patient was seen in clinic and complained of mild but persistent pleuritic chest pain. She was discovered to be hypoxic with exertion and was readmitted to the hospital. Associated symptoms included intermittent difficulty sleeping, dry cough and shortness of breath on exertion. She denied recent drug abuse, aspiration or suspicious ingestions. There was exposure to cats and chickens in the past month. Recent medications in addition to the antibiotics had included ferrous sulfate, lisinopril, tramadol, lamictal, warfarin (for her DVT), promethazine and omeprazole. Vital signs, including respiratory rate, were normal. Oxygen saturation was 98% while resting but dropped to 82% on exertion. Physical examination revealed an awake and alert teenager in no acute distress. Lungs were clear bilaterally although deep inspiration was inhibited secondary to chest pain. High resolution computed tomography (CT) scan on admission revealed a pattern of perilobular septal thickening with multifocal ground glass opacities (a ‘crazy paving’ pattern) in both lower lobes, and less extensively in the right middle lobe and lingula (Fig. 1A). Right lower lobe bronchoalveolar lavage fluid (BALF) showed numerous macrophages and positive fat stains in a pattern consistent with endogenous lipid deposition. PAS stain in BALF was negative. Surgical lung biopsy of the left upper lobe revealed hyperinflation, alveolar septal destruction and alveolar accumulation of foamy macrophages consistent with ELP and NSIP (Fig. 2A). There was no evidence of PAP on initial biopsy.
The Clinical Respiratory Journal (2016) • ISSN 1752-6981 2
C 2014 John Wiley & Sons Ltd V
(B)
Figure 1. Lipoid pneumonia with crazy paving pattern. (A) High resolution computed tomography (CT) scan of the chest on the day of admission showing combined pattern of smooth perilobular septal thickening with multifocal ground glass opacities or ‘crazy paving pattern’. (B) Chest CT on hospital day 16 demonstrating worsened appearance of patchy ground glass opacity and intralobular sepal thickening. Scale bar equal to 500 μm.
Over the next 8 weeks, she developed subcutaneous emphysema, continued chest pain, persistent and progressively worsening hypoxia, intermittent mild elevation of transaminases and pancreatic enzymes, pericarditis, pericardial effusions, polyarticular arthralgia and pulmonary hypertension. Her lung function with restrictive pattern continued to worsen and follow-up CT scans revealed wide-spread interstitial patchy ground glass opacity with intralobular sepal thickening involving all lung fields (Fig. 2B). She underwent an exhaustive diagnostic workup to identify the cause of her underlying ELP, including negative workups for surfactant protein gene mutations, Neiman Pick disease, juvenile idiopathic arthritis, 247 The Clinical Respiratory Journal (2014) • ISSN 1752-6981 © 2014 John Wiley & Sons Ltd
Lipoid pneumonia preceding alveolar proteinosis Antoon et al.
(A)
et al. Lipoid pneumonia preceding alveolarAntoon proteinosis
tion was felt to be contraindicated due to the ambiguity of her underlying diagnosis, her markedly elevated body mass index and her inability to wean from high dose corticosteroids and analgesics. She remained as an inpatient dependent on high flow oxygen, bi-level positive airway pressure and analgesics and died 10 months after admission. Autopsy of the lungs showed a definitive diagnosis of PAP (Fig. 2B).
Discussion
(B)
Figure 2. Histopathology of endogenous lipoid pneumonia and pulmonary alveolar proteinosis. (A) Lung biopsy histopathology demonstrating alveolar accumulation of foamy macrophages (arrows) consistent with endogenous lipoid pneumonia. (B) Lung histopathology at autopsy showed diffuse interstitial and alveolar pulmonary disease (with sparing of portion of left lower lobe), with abundant lipoproteinaceous granular debris filling the alveolar spaces. Diagnosis was confirmed using electron microscopy. Scale bar equal to 500 μm.
granulomatosis with polyangiitis and other autoimmune disorders. It was thought that her initial cellulitis was an initiating event for the presentation of an underlying connective tissue disease or immune disorder. Various empiric treatments, including antibiotics, antivirals, antifungals, immunosuppression and plasmapheresis did not elicit a therapeutic response. She partially responded to high dose corticosteroids and cyclophosphamide, but unfortunately, the deterioration in her lung function was not reversible. Repeat lung biopsy or bronchoscopy was not undertaken because of her degree of respiratory compromise. Lung transplanta248Clinical Respiratory Journal (2014) • ISSN 1752-6981 The © 2014 John Wiley & Sons Ltd
We report what we believe to be the first pediatric case of endogenous lipoid pneumonia and NSIP preceding the development of PAP. Initial biopsy specimens were evaluated by pulmonary pathologists from three separate academic institutions, and there was no evidence of PAP at that time. However, autopsy 10 months later revealed extensive PAP, believed to be the primary cause of death. Based on her multitude of systemic symptoms, negative family history of PAP and adolescent age, our patient likely had secondary PAP with an unknown triggering etiology. To the best of our knowledge, there are no reported cases of ELP or NSIP progressing to PAP in the literature. Surfactant protein deficiency can cause both NSIP and PAP, which presents with clinical symptoms early in life (2). There are three published studies of coexisting ELP and PAP . McDonald et al. reported a case of a 5 year old with recurrent aspiration who was found to have PAP and ELP on biopsy (3). Sato et al. reported of a case of an 18 year old with ELP and PAP, with PAP being much less extensive than ELP at time of autopsy (4). Fisher et al. pushed a series of eight patients with ELP and PAP (5). All of these patients had coexisting disease at time of diagnosis, with four patients having primarily ELP and two with moreextensive PAP on initial tissue sampling. Our patient’s disease progression was similar to one patient in the Fisher series, a 3 year old with lysinuric protein intolerance and glucose-6-phosphate dehydrogenase deficiency, who had mostly ELP on initial biopsy with more-extensive PAP on autopsy. However, our patient differed in age, presentation, associated symptoms and did not have signs of PAP on her initial biopsy. It is unclear whether a precipitating factor, such as a bacterial toxin or underlying autoimmune disease, resulted in independent development of ELP and PAP. Whole-lung lavage, which would have been feasible only with extracorporeal membrane oxygenation support, was not considered due to the negative prior workup for PAP. We speculate that ELP may be an early finding in the development of PAP, and we The Clinical Respiratory Journal (2016) • ISSN 1752-6981 3 C 2014 John Wiley & Sons Ltd V
Antoonpneumonia et al. Lipoid preceding alveolar proteinosis
recommend that PAP testing, including serum and BAL anti-GM-CSF antibody, be considered in pediatric patients with ELP or NSIP and subsequent further respiratory deterioration.
Acknowledgments We thank Drs William K. Funkhouser, H. Michael Jones and Nathan D. Montgomery for their help with histopathology.
References 1. Das M, Salzman GA. Pulmonary alveolar proteinosis: an overview for internists and hospital physicians. Hosp Pract (1995). 2010;38(1): 43–9. [Review]. 2. Brasch F, Griese M, Tredano M, et al. Interstitial lung disease in a baby with a de novo mutation in the SFTPC
The Clinical Respiratory Journal (2016) • ISSN 1752-6981 4
C 2014 John Wiley & Sons Ltd V
Lipoid pneumonia preceding alveolarAntoon proteinosis et al.
gene. Eur Respir J. 2004;24(1): 30–9. [Case Reports Comparative Study Research Support, Non-U.S. Gov’t Research Support, U.S. Gov’t, P.H.S. Review]. 3. McDonald JW, Roggli VL, Bradford WD. Coexisting endogenous and exogenous lipoid pneumonia and pulmonary alveolar proteinosis in a patient with neurodevelopmental disease. Pediatr Pathol. 1994;14(3): 505–11. Affiliated with the International Paediatric Pathology Association. [Case Reports]. 4. Sato K, Takahashi H, Amano H, Uekusa T, Dambara T, Kira S. Diffuse progressive pulmonary interstitial and intra-alveolar cholesterol granulomas in childhood. Eur Respir J. 1996;9(11): 2419–22. [Case Reports]. 5. Fisher M, Roggli V, Merten D, Mulvihill D, Spock A. Coexisting endogenous lipoid pneumonia, cholesterol granulomas, and pulmonary alveolar proteinosis in a pediatric population: a clinical, radiographic, and pathologic correlation. Pediatr Pathol. 1992;12(3): 365–83. Affiliated with the International Paediatric Pathology Association. [Case Reports].
249 The Clinical Respiratory Journal (2014) • ISSN 1752-6981 © 2014 John Wiley & Sons Ltd
