Lipoid Pneumonia: an Overview

Expert Review of Respiratory Medicine

ISSN: 1747-6348 (Print) 1747-6356 (Online) Journal homepage: http://www.tandfonline.com/loi/ierx20

Lipoid pneumonia: an overview

Vijay Hadda & Gopi C Khilnani

To cite this article: Vijay Hadda & Gopi C Khilnani (2010) Lipoid pneumonia: an overview, Expert Review of Respiratory Medicine, 4:6, 799-807, DOI: 10.1586/ers.10.74

To link to this article: http://dx.doi.org/10.1586/ers.10.74

Published online: 09 Jan 2014.

Submit your article to this journal

Article views: 174

View related articles

Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalInformation?journalCode=ierx20

Download by: [Inova Fairfax Hospital] Date: 26 May 2016, At: 03:03 Review For reprint orders, please contact [email protected]

Lipoid pneumonia: an overview

Expert Rev. Resp. Med. 4(6), 799–807 (2010)

Vijay Hadda1 and Lipoid pneumonia is an uncommon disease caused by the presence of lipid in the alveoli. It is Gopi C Khilnani†1 classified into two major groups, depending on whether the lipid/oil in the respiratory tract is from an exogenous (exogenous lipoid pneumonia) or endogenous/idiopathic (endogenous 1Department of Medicine, All India Institute of Medical Sciences, lipoid pneumonia) source. The usual presentation occurs with insidious onset and nonspecific New Delhi, 110029 India respiratory symptoms such as dyspnea and/or cough. The main radiological findings include †Author for correspondence: airspace consolidations, ground-glass attenuation, airspace nodules and ‘crazy-paving’ pattern. Tel.: +91 112 658 3488 However, the radiological appearance of the disorder can mimic many other lung diseases, Fax: +91 112 658 8641 [email protected] including carcinoma. Owing to the nonspecific clinical presentation and radiological features, the diagnosis is often missed or delayed. Pathologically, lipoid pneumonia is a chronic foreign body reaction to fat, characterized by lipid-laden macrophages. Diagnosis of this disease requires a high index of suspicion and can be confirmed by demonstration of lipid-laden macrophages in respiratory samples such as sputum, bronchoalveolar lavage fluid or fine-needle aspiration cytology/biopsy from lung lesions. Treatment protocols for this illness are poorly defined.

Keywords: endogenous lipoid pneumonia • exogenous lipoid pneumonia • lipid-laden macrophages • lipoid pneumonia Lipoid pneumonia is an uncommon form of may be avoided. Importantly, the progression pneumonia characterized by the presence of may be halted, or at least slowed, by preventing intra-alveolar lipid and lipid-laden macrophages exposure to the offending agent. on microscopy. It was first reported in 1925 by Lipoid pneumonia has been classified into Laughlen in association with laxative use [1]. exogenous and endogenous lipoid pneumo- Subsequently, there were many reports of this nia, based on the source of the lipid exposure. pneumonia caused by inhalation or aspiration Exogenous lipoid pneumonia is related to inha- of a fatty substance during the first half of the lation or aspiration of fatty substances, whereas 20th Century [2–5]. Lipoid pneumonia has been in endogenous lipoid pneumonia, intra-alveolar reported under different names, such as paraffin- lipid accumulation occurs as a result of obstruc- oma, cholesterol pneumonia and lipid granulo tion, chronic lung infection/disease or a lipid Downloaded by [Inova Fairfax Hospital] at 03:03 26 May 2016 matosis, denoting its association with inhala- storage disorder. The aim of this article is to tion or ingestion of various substances, such as acquaint physicians with both these entities and petroleum jelly, mineral oils and nasal drops, discuss the management options. and even intravenous injection of olive oil [6–14]. Its precise incidence is not well known, however, Exogenous lipoid pneumonia one autopsy study from the USA has reported a Historically, the first description of exogenous frequency of 1.0–2.5% [15]. Although awareness lipoid pneumonia was given by Laughlen in four about this disease has increased, many physi- patients with a history of chronic laxative and cians are still unfamiliar with this condition, nasal drop use [1]. Exogenous lipoid pneumonia which may be responsible for underdiagnosis. is more commonly reported in the literature. Lack of specific clinical or radiological features may lead to further missed or delayed diagnoses. Risk factors for exogenous Therefore, awareness of this type of pneumonia lipoid pneumonia is important. Diagnosis can be established by Lipoid pneumonia as an unusual cause of respi- demonstrating lipid-laden macrophages in vari- ratory symptoms has been reported in all age ous specimens such as sputum, bronchoalveolar groups. Initially, it was reported predominantly lavage (BAL) or lung biopsy. If diagnosed at the in children – often with local anatomic defects, right time, the unnecessary use of antibiotics such as cleft palate, or in debilitated adults, but

several reports indicate that it can also occur in healthy indi Chronic exogenous lipoid pneumonia is more common and viduals [9,16]. The aspiration or inhalation of fatty substances results from the repeated aspiration of mineral oils/fatty sub- is a central causative factor for exogenous lipoid pneumonia. stances of animal origin [9]. It usually presents with dyspnea and/or Aspiration may be due to abnormality in deglutition (anatomical cough. Less commonly described clinical features include chest or functional pharyngeal and esophageal abnormality), or neu- pain, hemoptysis and intermittent fever, which may be related to romuscular diseases affecting pharyngeal motility or the cough the inflammatory reaction to oil or to secondary infection [32]. reflex. In normal subjects, aspiration may be occupation related Some authors have also described weight loss in these patients (e.g., fire-eater) [17,18] or due to trivial habits such as use of oil- [9,15]. Physical examination findings are usually normal, although based laxatives, lip balm, lip gloss and petroleum jelly, among one may find dullness on percussion, crackles, wheezes or rhonchi. others [9,19,20]. Siphoning of various mineral oils (e.g., diesel) from In long-standing progressive disease, physical findings related to containers is a common practice in India and may be a risk factor chronic hypoxia, such as clubbing, can develop [9]. for lipid aspiration [21]. Many traditional folk remedies such as Blood investigation results are usually normal. However, leuko the use of oily nasal drops, forceful animal fat feeding, such as cytosis and an increased erythrocyte sedimentation rate may ‘ghee’, to establish regular bowel habits or transnasal administra- occur, especially when complicated by infection. Pulmonary tion of medicines to treat cough and cold have been described as function test results have shown a restrictive pattern but may also risk factors for exogenous lipoid pneumonia in infants and small be normal [32,33]. children [22,23]. Other examples of such therapies are use of sesame oil to flush nasal secretions (in India) and to relieve small bowel Radiological features of exogenous lipoid pneumonia obstruction due to Ascaris lumbricoides (in Brazil) [24,25]. Aspiration On radiological imaging, diverse findings have been described that has also been reported as an iatrogenic complication following can mimic many other lung diseases including carcinoma, pneu- bronchography using the dye propyliodone (now rarely performed) monia, acute respiratory distress syndrome or a localized granu- and during nasogastric tube feeding [26,27]. loma [34–36]. Radiologically, manifestations of acute exogenous lipoid pneumonia may be seen as early as 30 min after the episode Clinical features of exogenous lipoid pneumonia of aspiration or inhalation, and in most patients within 24 h [37]. The usual presentation of exogenous lipoid pneumonia occurs The typical findings include homogenous dense consolidation, alongside dyspnea and/or cough, in a similar manner to other often with air bronchograms and sometimes a fine, ‘spun glass’ lung diseases. On the basis of onset of the disease it can have appearance may be observed [34]. The most common findings acute or chronic presentation. Acute exogenous lipoid pneumonia described on CT scan include airspace consolidations, areas of is uncommon and may simulate infectious pneumonia with fever, ground-glass attenuation, airspace nodules and ‘crazy-paving’ with or without cough [21,28]. It is typically caused by massive pattern [38]. Consolidations are usually heterogeneous and their exposure to mineral oils/animal fats [29–31]. negative density values, as low as -30 to -150 HU, are a diagnostic criteria for lipoid pneumonia (Figure 1). However, superimposed inflammation may act as a confounding factor and may increase the attenuation values of the lesion [15,39]. Involvement may be diffuse or focal, and unilateral or bilateral, however, Downloaded by [Inova Fairfax Hospital] at 03:03 26 May 2016 unilateral pneumonic consolidation with lower lobe predilection is more commonly reported [34,35,38,40–42]. Other radiological abnormalities that can be seen in these patients include pneumatoceles, pneumo- mediastinum, pneumothorax and pleural effusions [37,42,43]. Occasionally, one may also find cavitation [44,45]. Pneumatoceles usually develop within regions of ground- glass opacity or consolidation and usually manifest within 2–30 days of aspiration or inhalation. These are more commonly seen in patients with massive exposure to mineral oils [46]. Pneumothorax and pneumomedia stinum are rare and have been reported to Figure 1. CT scan of the chest of a patient with acute exogenous lipoid occur within 4 days after hydrocarbon aspi- pneumonia. A large consolidation with foci of low attenuation values as indicated (arrow). ration [39]. Importantly, they are associated Reproduced from [21]. with a poor prognosis [39].

800 Expert Rev. Resp. Med. 4(6), (2010) Lipoid pneumonia: an overview Review

The radiologic manifestations of acute exogenous lipoid pneu- or inhalation (volatile hydrocarbons). Few mineral oils such as monia usually show a partial to complete resolution over time gasoline can cause lung injury even after intravenous injection after stopping exposure to lipids. Resolution of opacities is usually [57]. In the case of exogenous lipoid pneumonia due to inhala- observed within 2 weeks to 8 months, however, they may be pro- tion/aspiration, mineral oils/fat enter the tracheobronchial tree gressive or static in some cases, even after stopping the exposure and without stimulating the cough reflex and impair the mucociliary symptomatic improvement [3,15,39]. There can be scarring of lung transport system. The mechanism of lung injury after intravenous parenchyma, which can cause persistence of radiological shadow. injection is complex. It has been suggested that the lung is the first Similar to acute exogenous lipoid pneumonia, the most fre- capillary bed encountered during circulation, thereby bearing the quent radiological feature of chronic exogenous lipoid pneumonia majority of the damage [58,59]. Once inside the alveoli, it is dif- is ground-glass opacity or consolidation involving one or more ficult to expectorate the lipid. This situation may be complicated segments, typically with a peribronchovascular distribution and by associated neurological and gastrointestinal disorders affecting predominant involvement of the lower lobes [39]. Fibrosis and swallowing, palatal or cough reflex. Once in the alveoli, oil is coalescence of oil can result in nodules and masses with irregular taken up by macrophages after emulsification. Because alveolar margins, closely mimicking lung cancer [34,35]. The most commonly macrophages cannot metabolize the fatty substance, the oil is described feature is alveolar consolidations of low attenuation val- repeatedly released into the alveoli after death of the macrophages ues, ground-glass opacities with thickening of intralobular septa [60]. The oil released illicits a giant-cell granulomatous reaction (crazy-paving pattern) or alveolar nodules (Figures 2 & 3) [15,22,42,47]. (hence also called lipid granulomatosis), chronic inflammation, Magnetic resonance imaging may reveal high signal intensity on and alveolar and interstitial fibrosis. Evolution of lesions with time T1-weighted imaging consistent with lipid content [19,42,48–50]. has been described [49]. Fresh lesions show alveolar infiltration by Characteristically, chronic exogenous lipoid pneumonia mani- lipid-laden macrophages and almost normal alveolar walls and fests itself as a fat-containing mass [15]. Although the mass is septa. Advanced lesions show larger vacuoles and inflammatory typically irregular or spiculated due to chronic inflammation and infiltrates in alveolar walls, bronchial walls and septa. The fibro- fibrosis, the presence of fat in the mass, with a few exceptions, is sis and parenchymal destruction around large lipid-containing a diagnostic feature of exogenous lipoid pneumonia. Other con- vacuoles are features of the oldest lesions. Special staining tech- ditions that can show similar features are hamartomas and lung niques (such as oil red O and Sudan black) can demonstrate more metastases from primary extrathoracic sarcomas, such as chondro- effectively whether the vacuoles are filled with lipid. sarcomas or liposarcomas [39]. Cavitation and calcification of the mass can occasionally occur [9]. Diagnosis of exogenous lipoid pneumonia Other features of chronic exogenous lipoid pneumonia include Diagnosis of lipoid pneumonia is often difficult, because it is not single or multiple nodules or masses, with or without fat enclosed. routinely suspected at the time of presentation. Quite often, cases In the absence of fat (an infrequent finding), the nodules or are treated as an infective community-acquired pneumonia and masses can be indistinguishable from other lung masses [51–53]. Recently, 2-deoxy-2-F- fluoro-d-glucose (FDG) and 3’-deoxy-3’-F- fluorothymidine (FLT) positron emission tomography (PET) have also been used for the diagnosis of chronic exogenous lipoid Downloaded by [Inova Fairfax Hospital] at 03:03 26 May 2016 pneumonia, although it should be noted that it can be misinterpreted as malignancy [54,55]. The radiological manifestations of chronic exogenous lipoid pneumonia can improve slowly over time, however, in many patients there will be progression of opacity even if the exposure to vegetable or mineral oils or animal fats is discontinued [15]. Fibrosis and destruction of normal lung architecture can result in cor pulmonale [56].

Pathophysiology of exogenous lipoid pneumonia Pathologically, lipoid pneumonia is thought to be caused by a chronic foreign body reaction to fatty substances in the alveoli. The Figure 2. CT scan of a chest showing a mass lesion (black arrow) and mechanisms by which lipids reach alveoli crazy-paving pattern (white arrow) adjacent to it. are aspiration (nonvolatile hydrocarbons) Image provided by Ami Rubinowitz and Erica Herzog, Yale University (CT, USA).

www.expert-reviews.com 801 Review Hadda & Khilnani

Therefore, BAL fluid is the preferred sample for this. BAL may reveal turbid or whitish fluid with fat droplets visible at the surface [62]. Frozen samples should be examined by various stains to discriminate types of oils. Chromatography and infrared spectroscopy may also be used. Transthoracic fine-needle aspiration cytology may be diagnostic but false-negative results can occur [63]. In some cases, transbronchial lung biopsy or even surgical biopsy may be required [64,65]. Although most of the reports have used fat-laden macrophage as a diagnostic marker for lipoid pneumonia, its specificity has been questioned by some authors [66,67]. Therefore, diagnosis of exogenous lipoid pneumonia should be based on the triad of history of mineral oil ingestion, com- patible radiological findings, and presence of intra-alveolar lipids and/or lipid-laden macrophages.

Figure 3. CT scan of a chest demonstrating areas of ground-glass opacity Endogenous lipoid pneumonia superimposed on interlobular septal thickening (crazy-paving pattern) on the Endogenous lipoid pneumonia was first right side. described by McDonald et al. in 1949 as Images provided by Edson Marchiori, Fluminense Federal University (Rio de Janeiro, Brazil). ‘obstructive pneumonitis’ in patients with lung neoplasms [68]. The obstructive pneu- an alternative diagnosis is only considered when the patient does monitis was characterized by the presence of bronchial obstruction not respond to therapy. This is also because there are no diag- and the accumulation of lipid-filled macrophages. Macroscopically, nostic radiological features on the chest radiograph. Therefore, there is parenchymal consolidation that has a characteristic yellowish a detailed history of exposure to fatty substances should be taken to achieve early diagnosis. In a patient at risk of aspiration/ inhalation of mineral oils, an early CT scan is very useful for providing further clues to the diagnosis of lipoid pneumonia. Once suspected, the diagnosis is not diffi- Downloaded by [Inova Fairfax Hospital] at 03:03 26 May 2016 cult. The diagnosis of lipoid pneumonia is confirmed by detecting intra-alveolar lipid and lipid-laden macrophages in respiratory specimens. Various specimens that may be used for confirmation of the diagnosis include sputum, BAL, transthoracic fine-needle aspiration cytology or biopsy from the lesion (Figure 4). A sputum sample is easy to obtain, however, many patients do not produce any sputum and repeated attempts may be required to obtain a repre- sentative sample [39]. Furthermore, sputum examination has questionable reliability and lipid-laden macrophages in sputum have been demonstrated in the absence of lipoid Figure 4. Centrifuged bronchoalveolar lavage (hematoxylin and eosin pneumonia [61]. Today BAL is widely avail- staining) fluid showing multiple lipid-laden macrophages (appearing as able and many studies have proven its utility vacuoles [arrows]). Reproduced from [21]. in the diagnosis of lipoid pneumonia [38,39].

802 Expert Rev. Resp. Med. 4(6), (2010) Lipoid pneumonia: an overview Review

discoloration due to the accumulation of lipid in the alveoli, hence result of transbronchial dissemination of breakdown products of also called ‘golden pneumonia’ [69]. Histologically, there is an accu- cancer cells, especially those of poorly differentiated adenocarci- mulation of lipid-filled macrophages and eosinophilic proteinaceous noma cells and secretions including mucin [70]. Another mechanism material derived from degenerating cells, including surfactant from that has been suggested involves the anoxic tissue injury stimulat- type II pneumocytes, in the alveoli distal to the bronchial obstruc- ing various enzymes such as phospholipases and mono-oxygenases, tion, hence named ‘cholesterol pneumonia’. Endogenous lipoid which in turn cause modification of low-density lipoprotein choles- pneumonia has been further classified into three types based on terol. This modified low-density lipoprotein cholesterol enhances bronchial obstruction: type I lipoid pneumonia, localized to the lipid uptake by alveolar macrophages similar to atherogenesis [80–82]. lung parenchyma distal to an airway obstructed by a tumor; type II As for the contribution of infectious changes to endogenous lipoid lipoid pneumonia, with features of type I lipoid pneumonia and pneumonia, infection is generally localized in airways because the consecutively spreading to the adjacent segment whose airway is surrounding lung is already consolidated by the noninfectious not affected; and type III lipoid pneumonia, with features of type II inflammatory changes, limiting the spread of bacteria[71] . lipoid pneumonia and spreading to isolated segments [70]. Initially, endogenous pneumonia was thought to be the result of the obstruc- Diagnosis of endogenous lipoid pneumonia tive pneumonitis caused by infection mainly in the obstructed bron- Endogenous lipoid pneumonia typically manifests radiologically chus [68,71,72]. Later, however, many researchers observed the fact as consolidative opacities with or without a central obstructing that the condition is indeed due to a noninfectious process such as lesion (Figure 5) [70]. However, unlike exogenous lipoid pneumonia, physical or chemical effects of airway blockage [71,72]. the accumulation of lipid-rich cellular debris does not manifest radiologically as lipid-containing opacities with low attenuation Risk factors for endogenous lipoid pneumonia typical of lipid [39]. The diagnosis of endogenous lipoid pneumo- Historically, endogenous lipoid pneumonia has typically been nia is made on histopathology characteristically demonstrating reported in association with bronchial obstruction in patients lipid-laden macrophages similar to exogenous lipoid pneumonia. with non-small-cell lung cancers. However, it can also occur as a Polarized light microscopy after staining with sulfuric acid and manifestation of infection and other diseases that are not associ- acetic acid (Schultz stain) usually reveals cholesterol crystals, a ated with bronchial obstruction. Recently, this disease has been finding indicative of endogenous lipoid pneumonia. reported in a patient with repetitive episodes of fungal pneumonia [73]. Endogenous lipoid pneumonia has been described in associa- Treatment of lipoid pneumonia tion with pulmonary alveolar proteinosis where the alveoli are Treatment of lipoid pneumonia is not well studied and published usually filled with protein and lipid material resembling surfac- experience is only with case reports [83,84]. In case of exogenous tant [69]. Pulmonary alveolar proteinosis typically manifests on lipoid pneumonia, avoiding ongoing exposure and providing CT scan as ground-glass opacities, often with superimposed thickening of the interlobular and intralobular interstitia (crazy-paving pattern) [69]. Niemann-Pick disease, a lipid-storage disorder in which accumulation of intra-alveolar and interstitial fat-laden macrophages and sphingo- Downloaded by [Inova Fairfax Hospital] at 03:03 26 May 2016 myelin occurs, is also within the spectrum of endogenous lipoid pneumonia [74]. There are many other conditions that may be associated with endogenous lipoid pneumonia such as sclerosing cholangitis, bronchiolitis obliterans, necrotizing granulomatosis and connective tissue disease [75–78].

Pathophysiology of endogenous lipoid pneumonia The pathogenesis of endogenous lipoid pneumonia is complex and has been thought to be related to several mechanisms, such as retained epithelial secretion, cell breakdown, leakage from vessels, prolonged hypoxia, Figure 5. CT scan of the chest of a patient with undifferentiated connective and local oxygen and carbon dioxide ten- tissue disease and endogenous lipoid pneumonia. The CT scan shows a nonspecific sion [71,72,79]. It has also been suggested that atelectatic area in the right lung and infiltrates in the left lung. endogenous lipoid pneumonia may be a Image provided by Zsolt Barta, University of Debrecen (Hungary).

www.expert-reviews.com 803 Review Hadda & Khilnani

supportive care is the mainstay of treatment. As anti-inflammatory lipoid pneumonia. Clinical and radiological presentations are agents, corticosteroids appear promising as a therapeutic option. diverse, therefore, in suspected cases histopathological/cytological One trial of corticosteroids in children with mild-to-moderate examination is mandatory to diagnose this condition. Treatment, lipoid pneumonia did not show any clinical or radiological ben- although not well defined, differs significantly from other causes of efits[85] . In adults, there are anecdotal reports of systemic cortico pneumonia, hence greater awareness of this condition is required. It steroid use to slow the inflammatory response [21,86]. However, should be considered as a differential diagnosis in all patients with corticosteroids are not indicated in all cases and should only be pneumonia and focus should be on elucidating their risk factors. used if the lung injury is severe and ongoing. There are reports of lipoid pneumonia being successfully treated with immuno- Five-year view globulins [87] and whole-lung lavage [88–91]. Repeated whole-lung Owing to its nonspecific symptoms and radiological features, lavage is especially useful in children [90,91]. Some authors have lipoid pneumonia often remains undiagnosed or diagnosis is described resection of nodules and masses in these cases [22,92]. delayed. However, with recent multiple publications on this Surgical resection is usually unwarranted as lipoid pneumonia is topic, we expect increased awareness and more frequent diagno- typically indolent and may regress spontaneously. Resection, how- sis of this disease. The detailed history of exposure to a variety ever, may be performed in cases where there is a high suspicion of substances is often missed in the management of community- of cancer [33]. Similarly, surgery seems a logical therapy in cases acquired pneumonia. Inclusion of this aspect in clinical care of of post-obstructive lipoid pneumonia. patients with pneumonia will further improve the diagnosis rate. Prognosis of lipoid pneumonia is usually indolent, however, it Lipoid pneumonia, although uncommon, should be considered in may also be progressive. Risk factors for progressive disease are all cases of respiratory symptoms and lung shadows. This condi- concurrent debilitating illness and continued exposure to min- tion further emphasizes the importance of proper collection of eral oil. Patients may show persistent or progressive radiologi- respiratory samples and subjecting them to cytological evaluation cal abnormalities despite symptomatic relief [9]. In addition, this besides microbiological evaluation. Accurate diagnosis will pre- may be complicated by superinfection with microorganisms such vent unnecessary use of expensive antibiotics and lead to better as Mycobacterium chelonei, Mycobacterium fortuitum and other management. With more frequent diagnosis of this disease, we bacteria [93,94]. Colonization by Cryptococcus is also reported [32]. may expect some data on routine examination of these samples Protracted exposure may cause respiratory insufficiency and may for lipid-laden macrophages. lead to cor pulmonale [56]. Hypercalcemia is one of the uncom- Since the disease is uncommonly diagnosed, there are no sys- mon complications of granulomatous reaction such as in TB and tematically conducted trials using corticosteroids. With increased sarcoidosis [95]. Association of lipoid pneumonia with lung cancer awareness and more frequent diagnosis, we can expect more is also reported in a few cases [96,97]. data regarding the role of various treatment modalities such as corticosteroids and repeated BAL. Expert commentary Lipoid pneumonia is an uncommon disease characterized patho- Financial & competing interests disclosure logically by the presence of lipid-laden macrophages in respira- The authors have no relevant affiliations or financial involvement with any tory specimens. It has been classified further as exogenous or organization or entity with a financial interest in or financial conflict with endogenous lipoid pneumonia. Inhalation or aspiration of fatty the subject matter or materials discussed in the manuscript. This includes substances is the most important risk factor in case of exogenous employment, consultancies, honoraria, stock ownership or options, expert Downloaded by [Inova Fairfax Hospital] at 03:03 26 May 2016 lipoid pneumonia. Bronchial obstruction and other miscellaneous testimony, grants or patents received or pending, or royalties. lung conditions have been reported as risk factors for endogenous No writing assistance was utilized in the production of this manuscript.

Key issues • Lipoid pneumonia is not easily diagnosed, since its clinical features are nonspecific. • Lipid in the alveoli is central to the pathogenesis of lipoid pneumonia. • The source of lipid may be known (inhalation/aspiration) in the case of exogenous lipoid pneumonia or unknown (due to the breakdown of various cell products) in the case of endogenous lipoid pneumonia. • Radiological features may mimic other lung diseases; however, CT scan plays an important role in diagnosis of lipoid pneumonia. • The diagnosis of lipoid pneumonia requires a high degree of suspicion and confirmation by demonstration of lipid-laden macrophages in respiratory specimens. • The useful respiratory specimens are bronchoalveolar lavage and fine-needle aspiration cytology/biopsy from lung lesion. • There are no guidelines available for the treatment of this disease. • Repeated bronchoalveolar lavage seems a safe and effective treatment modality for this condition, though more studies are required before recommending it as a definite therapy. Similarly, anecdotal case reports support the use of corticosteroids in acute exogenous lipoid pneumonia. Again, the evidence is not enough to recommend it in all patients. • The course of the disease is usually indolent with only few complications.

804 Expert Rev. Resp. Med. 4(6), (2010) Lipoid pneumonia: an overview Review

References 13 Mydlowski T, Malong P, Wiatr E. CT findings in lipoid pneumonia in infants Papers of special note have been highlighted as: [Exogenous lipoid pneumonia – case following aspiration of mineral oil used in • of interest report]. Pneumonol. Alergol. Pol. 72(5–6), the treatment of partial small bowel •• of considerable interest 214–216 (2004). obstruction by Ascaris lumbricoides. Pediatr. Radiol. 15(3), 157–160 (1985). 1 Laughlen GF. Studies on pneumonia 14 Brown AL. Lipoid pneumonia resulting following naso-pharyngeal injection of oil. from a dermoid cyst; case report. J. Thorac. 26 McDonald JR, Hodgson CH. The problem Am. J. Pathol. 1, 407–414 (1925). Surg. 20(2), 260–265 (1950). of lipoid pneumonia or granuloma of the lung. Med. Clin. North Am. New York 2 Adams FD, Pittman H. Lipid pneumonia 15 Baron SE, Haramati LB, Rivera VT. 989–996 (1954). of right middle lobe. N. Engl. J. Med. Radiological and clinical findings in acute 241(15), 579–582 (1949). and chronic exogenous lipoid pneumonia. 27 Wolfson BJ, Allen JL, Panitch HB, J. Thorac. Imaging 18(4), 217–224 (2003). Karmazin N. Lipid aspiration pneumonia 3 Baron E. Lipoid pneumonia due to the use due to gastroesophageal reflux. A of mineral oil as a laxative. VA Med. Mon. •• Retrospective study of 15 patients with complication of nasogastric lipid feedings. 77(9), 448–450 (1950). both acute and chronic exogenous lipoid Pediatr. Radiol. 19(8), 545–547 (1989). 4 Berg R Jr, Burford TH. Pulmonary pneumonia, which has shown that only 28 Fournier P, Aerts J, Damade R, Pasquier P. paraffinoma (lipoid pneumonia); a critical patients with chronic lipoid pneumonia [A rare cause of inflammatory syndrome: study. J. Thorac. Surg. 20(3), 418–428 had masses on CT scan. It also showed lipoid pneumonia]. Presse Med. 19(38), (1950). that acute exogenous lipoid pneumonia had better radiological clearance than 1768–1769 (1990). 5 No authors listed. WEEKLY 29 Aibar Arregui MA, Laborda Ezquerra K, clinicopathological exercise: lipoid chronic lipoid pneumonia. Conget Lopez F. [Lipoid pneumonia related pneumonia (paraffinoma of lung).N. Engl. 16 Meltzer E, Guranda L, Perelman M, to an accidental aspiration of gas-oil]. An. J. Med. 246(23), 909–912 (1952). Krupsky M, Vassilenko L, Sidi Y. Lipoid Med. Interna 24(4), 187–189 (2007). 6 Hoffman LR, Yen EH, Kanne JP, pneumonia: a preventable form of 30 Bernabeu Mora R, Mendez Martinez P, Effmann EL, Gibson RL, Van Niel CW. drug-induced lung injury. Eur. J. Intern. Abellan Martinez MC, Polo Garcia LA, Lipoid pneumonia due to Mexican folk Med. 16(8), 615–617 (2005). Lorenzo Cruz M, Sanchez Gascon F. remedies: cultural barriers to diagnosis. 17 Kitchen JM, O’Brien DE, McLaughlin [Acute lipoid pneumonia caused by Arch. Pediatr. Adolesc. Med. 159(11), AM. Perils of fire eating. An acute form of accidental aspiration of vaseline used in 1043–1048 (2005). lipoid pneumonia or fire eater’s lung. nasogastric intubation]. Arch. Thorax 63(5), 401, 39 (2008). 7 Costa AS, Noya R, Calvo TC, Severo R, Bronconeumol. 36(8), 485–487 (2000). Afonso A. [Exogenous lipoid pneumonia 18 Seaton A. Lipoid pneumonia in a fire 31 Facon D, Coumbaras J, Bigot E, Bahlouli – case report]. Rev. Port. Pneumol. 11(6), breather. Occup. Med. (Lond.) 60(5), 406 F, Boissonnas A, Bellin MF. Acute 567–572 (2005). (2010). hydrocarbon pneumonia after white spirit 8 Chauveau R, Medart L, Ghaye B. 19 Becton DL, Lowe JE, Falletta JM. Lipoid aspiration: sequential HRCT findings.Eur. [Exogenous lipoid pneumonia: a simple pneumonia in an adolescent girl secondary Radiol. 15(1), 31–33 (2005). diagnosis?]. Rev. Med. Liege 60(10), to use of lip gloss. J. Pediatr. 105(3), 32 Subramanian S, Kherdekar SS, Babu PG, 799–804 (2005). 421–423 (1984). Christianson CS. Lipoid pneumonia with 9 Gondouin A, Manzoni P, Ranfaing E et al. 20 Gurell MN, Kottmann RM, Xu H, Sime Cryptococcus neoformans colonisation. Exogenous lipid pneumonia: a retrospective PJ. Exogenous lipoid pneumonia: an Thorax 37(4), 319–320 (1982). multicentre study of 44 cases in France. unexpected complication of substance 33 Simmons A, Rouf E, Whittle J. Not your Eur. Respir. J. 9(7), 1463–1469 (1996). abuse. Ann. Intern. Med. 149(5), 364–365 typical pneumonia: a case of exogenous

Downloaded by [Inova Fairfax Hospital] at 03:03 26 May 2016 (2008). •• In this retrospective study, authors have lipoid pneumonia. J. Gen. Intern. Med. described the clinical, radiological and 21 Hadda V, Khilnani GC, Bhalla AS, Mathur 22(11), 1613–1616 (2007). S. Lipoid pneumonia presenting as non laboratory features of 44 patients with 34 Hampton AO, Bickham CE Jr, Winship T. resolving community acquired pneumonia: exogenous lipoid pneumonia. Lipoid pneumonia. Am. J. Roentgenol. a case report. Cases J. 2, 9332 (2009). 10 Bhagat R, Holmes IH, Kulaga A, Murphy Radium Ther. Nucl. Med. 73(6), 938–949 F, Cockcroft DW. Self-injection with olive 22 Annobil SH, Benjamin B, Kameswaran M, (1955). Khan AR. Lipoid pneumonia in children oil. A cause of lipoid pneumonia. Chest 35 Felson B, Ralaisomay G. Carcinoma of the following aspiration of animal fat (ghee). 107(3), 875–876 (1995). lung complicating lipoid pneumonia. Am. Ann. Trop. Paediatr. 11(1), 87–94 (1991). 11 Hirata M, Morita M, Maebou A, Hara H, J. Roentgenol. 141(5), 901–907 (1983). 23 Hugosson CO, Riff EJ, Moore CC, Akhtar Yoshimoto T, Hirao F. [A case of 36 Lipinski JK, Weisbrod GL, Sanders DE. M, Tufenkeji HT. Lipoid pneumonia in exogenous lipoid pneumonia probably due Exogenous lipoid pneumonitis: pulmonary infants: a radiological–pathological study. to domestic insecticide]. Nihon Kyobu patterns. AJR Am. J. Roentgenol. 136(5), Pediatr. Radiol. 21(3), 193–197 (1991). Shikkan Gakkai Zasshi 31(10), 1317–1321 931–934 (1981). (1993). 24 Balakrishnan S. Lipoid pneumonia in 37 Haas C, Lebas FX, Le Jeunne C, infants and children in South India. Br. 12 Alaminos Garcia P, Colodro Ruiz A, Lowenstein W, Durand H, Hugues FC. Med. J. 4(5888), 329–331 (1973). Menduina Guillen MJ, Banez Sanchez F, [Pneumopathies caused by inhalation of Perez Chica G. [Exogenous lipoid 25 de Oliveira GA, Del Caro SR, Bender hydrocarbons: apropos of 3 cases]. Ann. pneumonia. Presentation of a new case]. Lamego CM, Mercon de Vargas PR, Med. Interne (Paris) 151(6), 438–447 An. Med. Interna 22(6), 283–284 (2005). Vervloet VE. Radiographic plain film and (2000).

www.expert-reviews.com 805 Review Hadda & Khilnani

38 Marchiori E, Zanetti G, Mano CM, Irion 49 Laurent F, Philippe JC, Vergier B et al. 62 Levade T, Salvayre R, Dongay G et al. KL, Daltro PA, Hochhegger B. Lipoid Exogenous lipoid pneumonia: HRCT, MR, Chemical analysis of the bronchoalveolar pneumonia in 53 patients after aspiration and pathologic findings.Eur. Radiol. 9(6), washing fluid in the diagnosis of liquid of mineral oil: comparison of high- 1190–1196 (1999). paraffin pneumonia.J. Clin. Chem. Clin. resolution computed tomography findings 50 Carette MF, Grivaux M, Monod B, Capeau Biochem. 25(1), 45–48 (1987). in adults and children. J. Comput. Assist. F, Lebreton C, Bigot JM. MR findings in 63 Gattuso P, Reddy VB, Castelli MJ. Tomogr. 34(1), 9–12 (2010). lipoid pneumonia. AJR Am. J. Roentgenol. Exogenous lipoid pneumonitis due to Vicks •• In this retrospective study, the authors 153(5), 1097–1098 (1989). Vaporub inhalation diagnosed by fine have described various high-resolution 51 Brody JS, Levin B. Interlobular septa needle aspiration cytology. Cytopathology computed tomography findings in patients thickening in lipid pneumonia. Am. J. 2(6), 315–316 (1991). with exogenous lipoid pneumonia. The Roentgenol. Radium Ther. Nucl. Med. 88, 64 Ferretti GR, Jankowski A, Rodiere M, authors have also compared the 1061–1069 (1962). Brichon PY, Brambilla C, Lantuejoul S. radiological findings in adults with that 52 Davis EW, Hampton AO, Bickham CE, CT-guided biopsy of nonresolving focal air of children. Winship T. Lipoid pneumonia simulating space consolidation. J. Thorac. Imaging 23(1), 7–12 (2008). 39 Betancourt SL, Martinez-Jimenez S, Rossi tumor. J. Thorac. Surg. 28(2), 212–219 SE, Truong MT, Carrillo J, Erasmus JJ. (1954). 65 de Albuquerque Filho AP. Exogenous lipoid Lipoid pneumonia: spectrum of clinical 53 Scully RE, Galdabini JJ, McNeely BU. pneumonia: importance of clinical history and radiologic manifestations. AJR Am. Case records of the Massachusetts General to the diagnosis. J. Bras. Pneumol. 32(6), J. Roentgenol. 194(1), 103–109 (2010). Hospital. Weekly clinicopathological 596–598 (2006). •• Excellent review of radiological exercises. Case 22 – 1977. N. Engl. J. Med. 66 Knauer-Fischer S, Ratjen F. Lipid-laden manifestations of both exogenous as well 296(22), 1279–1287 (1977). macrophages in bronchoalveolar lavage as endogenous lipoid pneumonia. 54 Tahon F, Berthezene Y, Hominal S et al. fluid as a marker for pulmonary aspiration. Pediatr. Pulmonol. 27(6), 419–422 (1999). 40 Lipinski JK, Weisbrod GL, Sanders DE. Exogenous lipoid pneumonia with unusual Exogenous lipoid pneumonitis. J. Can. CT pattern and FDG positron emission 67 Kazachkov MY, Muhlebach MS, Livasy Assoc. Radiol. 31(2), 92–98 (1980). tomography scan findings.Eur. Radiol. CA, Noah TL. Lipid-laden macrophage 12(Suppl. 3), S171–S173 (2002). index and inflammation in bronchoalveolar 41 Kennedy JD, Costello P, Balikian JP, lavage fluids in children.Eur. Respir. J. Herman PG. Exogenous lipoid pneumonia. 55 Kanaji N, Bandoh S, Takano K et al. 18(5), 790–795 (2001). AJR Am. J. Roentgenol. 136(6), 1145–1149 Positron emission tomography-positive (1981). squalene-induced lipoid pneumonia 68 McDonald JR, Harrington SW, Clagett confirmed by gas chromatography-mass OT. Obstructive pneumonitis of neoplastic 42 Brechot JM, Buy JN, Laaban JP, spectrometry of bronchoalveolar lavage origin; an interpretation of one form of Rochemaure J. Computed tomography and fluid.Am. J. Med. Sci. 335(4), 310–314 so-called atelectasis and its correlation magnetic resonance findings in lipoid (2008). according to presence of absence of sputum. pneumonia. Thorax 46(10), 738–739 J. Thorac. Surg. 18(1), 97–112 (1949). (1991). 56 Casey JF. Chronic cor pulmonale associated with lipoid pneumonia. JAMA 69 Gaerte SC, Meyer CA, Winer-Muram HT, 43 Weinberg I, Fridlender ZG. Exogenous 177, 896–898 (1961). Tarver RD, Conces DJ Jr. Fat-containing lipoid pneumonia caused by paraffin in an lesions of the chest. Radiographics 22, amateur fire breather.Occup. Med. (Lond.) 57 Domej W, Mitterhammer H, Stauber R, S61–S78 (2002). 60(3), 234–235 (2010). Kaufmann P, Smolle KH. Successful outcome after intravenous gasoline 70 Tamura A, Hebisawa A, Fukushima K, 44 Genereux GP. Lipids in the lungs: injection. J. Med. Toxicol. 3(4), 173–177 Yotsumoto H, Mori M. Lipoid pneumonia Downloaded by [Inova Fairfax Hospital] at 03:03 26 May 2016 radiologic–pathologic correlation. J. Can. (2007). in lung cancer: radiographic and Assoc. Radiol. 21(1), 2–15 (2010). 58 Guerguerian AM, Lacroix J. Pulmonary pathological features. Jpn J. Clin. Oncol. 45 Antico A, Gabrielli M, D’Aversa C, Musa injury after intravenous hydrocarbon 28(8), 492–496 (1998). M, Torri T. Lipoid pneumonia: a case of injection. Paediatr. Child Health 5(8), •• Authors in this study included 147 cavitary bilateral nodular opacity. 471–472 (2000). consecutive patients of lung cancer who Monaldi Arch. Chest Dis. 51(4), 296–298 (1996). 59 Bratton L, Haddow JE. Ingestion of underwent surgery. This study charcoal lighter fluid.J. Pediatr. 87(4), demonstrated endogenous lipoid 46 Bandla HP, Davis SH, Hopkins NE. 633–636 (1975). pneumonia in 29% of surgical specimens. Lipoid pneumonia: a silent complication of mineral oil aspiration. Pediatrics 103(2), 60 Russo R, Chiumello D, Cassani G, 71 Burke M, Fraser R. Obstructive pneumonitis: E19 (1999). Maiocchi G, Gattinoni L. Case of a pathologic and pathogenetic reappraisal. exogenous lipoid pneumonia: steroid Radiology 166(3), 699–704 (1988). 47 Miller GJ, Ashcroft MT, Beadnell HM, therapy and lung lavage with an emulsifier. Wagner JC, Pepys J. The lipoid pneumonia 72 Cohen AB, Cline MJ. In vitro studies of the Anesthesiology 104(1), 197–198 (2006). of blackfat tobacco smokers in Guyana. Q. foamy macrophage of postobstructive J. Med. 40(160), 457–470 (1971). 61 Parameswaran K, Anvari M, Efthimiadis endogenous lipoid pneumonia in man. Am. A, Kamada D, Hargreave FE, Allen CJ. Rev. Respir. Dis. 106(1), 69–78 (1972). 48 Carrillon Y, Tixier E, Revel D, Cordier JF. Lipid-laden macrophages in induced MR diagnosis of lipoid pneumonia. 73 Itoh Y, Segawa H, Kito K et al. Lipoid sputum are a marker of oropharyngeal J. Comput. Assist. Tomogr. 12(5), 876–877 pneumonia with chronic myelomonocytic reflux and possible gastric aspiration.Eur. (1988). leukemia. Pathol. Res. Pract. 205(2), Respir. J. 16(6), 1119–1122 (2000). 143–147 (2009).

806 Expert Rev. Resp. Med. 4(6), (2010) Lipoid pneumonia: an overview Review

74 Nicholson AG, Wells AU, Hooper J, 82 Evans AJ, Sawyez CG, Wolfe BM, •• Demonstrated the role of bronchoalveolar Hansell DM, Kelleher A, Morgan C. Connelly PW, Maguire GF, Huff MW. lavage in diagnosis and treatment of Successful treatment of endogenous lipoid Evidence that cholesteryl ester and lipoid pneumonia. pneumonia due to Niemann-Pick Type B triglyceride accumulation in J774 91 Sias SM, Daltro PA, Marchiori E et al. disease with whole-lung lavage. Am. J. macrophages induced by very low density Clinic and radiological improvement of Respir. Crit. Care Med. 165(1), 128–131 lipoprotein subfractions occurs by different lipoid pneumonia with multiple (2002). mechanisms. 34(5), 703–717 J. Lipid Res. bronchoalveolar lavages. Pediatr. Pulmonol. 75 Berghaus TM, Haeckel T, Wagner T, von (1993). 44(4), 309–315 (2009). Scheidt W, Schwaiblmair MG. Endogenous 83 Spickard A 3rd, Hirschmann JV. •• Demonstrated that multiple therapeutic lipoid pneumonia associated with primary Exogenous lipoid pneumonia. Arch. Intern. bronchoalveolar lavages are a safe and sclerosing cholangitis. Lancet 369(9567), Med. 154(6), 686–692 (1994). effective treatment modality of 1140 (2007). 84 Khilnani GC, Hadda V. Lipoid lipoid pneumonia. 76 Au WY, Lie AK, Cheng VC, Cheng LC, pneumonia: an uncommon entity. Indian Wang EP, Wong CF. Successful lung J. Med. Sci. 63(10), 474–480 (2009). 92 Bellenot F, Regnard JF, Babo P, Rojas- transplantation for post-BMT bronchiolitis Miranda A, Couffinhal JC, Levasseur P. • An overview of clinical, radiological [Pseudotumoral lipid pneumopathies. obliterans and lipoid pneumonia associated and management aspects of exogenous with atypical mycobacterium and Apropos of six cases]. Ann. Chir. 45(8), lipoid pneumonia. aspergillosis infection. J. Heart Lung 715–718 (1991). Transplant. 26(8), 870–872 (2007). 85 Marks MI, Chicoine L, Legere G, 93 Greenberger PA, Katzenstein AL. Lipid Hillman E. Adrenocorticosteroid treatment pneumonia with atypical mycobacterial 77 Meyer EC. [Necrotizing granulomatosis of hydrocarbon pneumonia in children – a with cholesterol pneumonitis diagnosed colonization. Association with allergic cooperative study. J. Pediatr. 81(2), during life]. Dapim Refuiim. 24(2), bronchopulmonary aspergillosis. Arch. 366–369 (1972). 175–178 (1965). Intern. Med. 143(10), 2003–2005 (1983). 86 Chin NK, Hui KP, Sinniah R, Chan TB. 94 Dixon C, Bolivar R, Katz R, McMurtrey 78 Barta Z, Szabo GG, Bruckner G, Szegedi Idiopathic lipoid pneumonia in an adult G. Endogenous lipoid pneumonia M. Lipoid pneumonia and Mycobacterium treated with prednisolone. Chest 105(3), associated with undifferentiated connective fortuitum pulmonary infection: successful 956–957 (1994). tissue disease (UCTD). Med. Sci. Monit. treatment with sulfisoxazole.Tex. Med. 7(1), 134–136 (2001). 87 Amato GM, Novara V, Amato G. [Lipid 81(3), 57–60 (1985). pneumonia. Favorable outcome after 95 Greenaway TM, Caterson ID. 79 Verbeken EK, Demedts M, Vanwing J, treatment with intravenous Deneffe G, Lauweryns JM. Pulmonary Hypercalcemia and lipoid pneumonia. immunoglobulins, steroids, cephalosporins]. phospholipid accumulation distal to an Aust. NZ J. Med. 19(6), 713–715 (1989). Minerva Pediatr. 49(4), 163–169 (1997). obstructed bronchus. A morphologic study. 96 Keshishian JM, Abad JM, Fuchs M. Lipoid Arch. Pathol. Lab. Med. 113(8), 886–890 88 Chang HY, Chen CW, Chen CY et al. pneumonia. Review with a report of a case (1989). Successful treatment of diffuse lipoid of carcinoma occurring within an area of pneumonitis with whole lung lavage. lipoid pneumonia. Ann. Thorac. Surg. 7(3), 80 Taki T, Nakazima T, Emi Y, Konishi Y, Thorax 48(9), 947–948 (1993). Hayashi A, Matsumoto M. Accumulation 231–234 (1969). of surfactant phospholipids in lipid 89 Ciravegna B, Sacco O, Moroni C et al. 97 Breton JL, Jeffredo Y, Ranfaing E, Clement pneumonia induced with Mineral oil lipoid pneumonia in a child F, Faure E, Garnier G. [Associated lipid methylnaphthalene. Lipids 21(9), 548–552 with anoxic encephalopathy: treatment by pneumonia and bronchiolo-alveolar (1986). whole lung lavage. Pediatr. Pulmonol. carcinoma]. Rev. Mal. Respir. 11(6), 23(3), 233–237 (1997). Downloaded by [Inova Fairfax Hospital] at 03:03 26 May 2016 596–598 (1994). 81 Tolle A, Kolleck I, Schlame M, Wauer R, Stevens PA, Rustow B. Effect of hyperoxia 90 Sias SM, Ferreira AS, Daltro PA, on the composition of the alveolar Caetano RL, Moreira Jda S, Quirico- surfactant and the turnover of surfactant Santos T. Evolution of exogenous lipoid phospholipids, cholesterol, plasmalogens pneumonia in children: clinical aspects, and vitamin E. Biochim. Biophys. Acta radiological aspects and the role of 1346(2), 198–204 (1997). bronchoalveolar lavage. J. Bras. Pneumol. 35(9), 839–845 (2009).