HK J Paediatr (new series) 2017;22:225-228

Lipoid Pneumonia Following Aspiration of Lorenzo's Oil in aChild with X-linked Adrenoleukodystrophy

KR CHEON, HJ CHO, SS KIM, YJ WOO

Abstract Background: Exogenous lipoid pneumonia (LP) is caused by the aspiration or inhalation of lipid substancesinto the respiratory tract. The clinical symptoms are non-specific and variable, ranging from asymptomaticto life-threatening. Since there is very limited disease-modifying treatment to prevent the onset or slowthe progression of X-linked adrenoleukodystrophy (X-ALD), Lorenzo's oil can be used, although itseffect is still controversial. Case presentation: Here, we report a case of LP in a 6-year-old boy withX-ALD who was treated with Lorenzo's oil. To our knowledge, this is the first case report demonstrating anassociation between Lorenzo's oil therapy and LP in a paediatric patient with X-ALD. Conclusions: Patientswith X-ALD suffer from various neurological deficits, including swallowing difficulty and oromotordysfunction. In X-ALD patients with oromotor dysfunctions are at high risk of LP while using Lorenzo'soil, where physicians should be aware and avoid if possible. This awareness can enable early diagnosis andtreatment of LP and improve prognosis by discontinuing exposure to the offending agent or to an appropriatetreatment.

Key words Adrenoleukodystrophy; Lipoid pneumonia; Lorenzo's oil

Department of Pediatrics, Chonnam National UniversityHospital, Chonnam National University Medical School,671 Jebongro Gwangju, 501-757, South Korea

KR CHEON MDHJ CHO MDYJ WOO MD

Department of Pathology, Chonnam National UniversityHospital, Chonnam National University Medical School,671 Jebongro Gwangju, 501-757, South Korea

SS KIM MD

Correspondence to: Dr. HJ CHO

Email: chhj98@gmail.com

Received May 9, 2016

Case Report

Background

Lipoid pneumonia (LP) is an uncommon disease causedby the presence and accumulation of lipid compounds inthe pulmonary tract and alveoli.1,2 The clinical symptoms

are non-specific, such as dyspnoea and/or cough andvariable, ranging from asymptomatic to as severe as life-threatening.1 It can be classified into endogenous andexogenous forms. Exogenous LP has various causes,including oils present in food, radiographic contrast media,and oil-based medications such as laxatives.2

Here, we report a case of LP occurring secondary totreatment with Lorenzo's oil in a patient with childhoodcerebral form X-linked adrenoleukodystrophy (X-ALD).To our knowledge, this is the first case report demonstratingan association between Lorenzo's oil therapy and LP in apaediatric patient with X-ALD.

Case Presentation

A 6-year-old boy was admitted to hospital presentingwith a 1-week history of cough and sputum. At the age of5 years, he was diagnosed with the cerebral form of X-ALDwith rapid regression and motor weakness. On admission,he could not walk or sit by himself however required per

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oral feeding without any gastric tube. Genetic analysisconfirmed the diagnosis by identifying an ABCD1 genemutation. At the time of the genetic analysis, increasedlevels of very long-chain fatty acids (VLCFAs) were alsodetected (C26:0 = 4.74 mmol/L (normal <1.30 mmol/L)and C26:0/C22:0 = 0.072 (normal <0.023)). Brain magneticresonance imaging (MRI) revealed bilateral hyperintenselesions involving the frontal and occipital periventricularwhite matter, internal capsule, genu and splenium of thecorpus callosum and corticospital tract. In addition, linearand nodular enhancements in the corpus callosum andinternal capsule were also noted. These findings werecompatible with ALD. As there is no disease-modifyingtreatment to prevent the onset or slow the progression ofthis disease, the parents of the patient were informed ofseveral treatment options including haematopoietic stem celltransplantation. However, the parents refused these options.Although the effect of Lorenzo's oil is still controversial,the patient had been taking 20 cc Lorenzo's oil twice dailyfor the last 3 months, together with supportive care andrehabilitation. Although his neurological status deteriorated,Lorenzo's oil was administered orally. While taking the oil,he had a history of frequent choking and coughing.

On physical examination, crackles were auscultatedbilaterally without any signs of chest retraction ortachypnoea and the saturation of O2 was 95~98% in roomair. Chest radiography showed multifocally increasedopacity in both lung fields (Figure 1A). High-resolutioncomputed tomography (HRCT) of the chest showed diffusebilateral ground glass opacity and smooth interstitial

thickening with a crazy-paving pattern in both lungs,predominantly in the posterior and lower lung zones. Thesefindings were compatible with LP (Figure 1B).

The patient underwent diagnostic bronchoscopy withbronchoalveolar lavage (BAL). The bronchoscopic findingsindicated no endobronchial lesions, but whitish secretionswere drained from the posterior segmental bronchi of theright upper lobe and superior segmental bronchi of the rightlower lobe and BAL was performed from this lesion.Bacterial, mycobacterial and fungal analyses of the BALfluid were negative, and the BAL fluid was also negativefor malignant cells.

The BAL fluid showed a milky whitish appearance. Oilred O staining demonstrated numerous lipid-ladenmacrophages (Figure 2). The patient was confirmed to haveLP and was hospitalised for 10 days with supportive care.His symptoms gradually improved and after the occurenceof LP, he discontinued taking Lorenzo's oil. Due to the earlydevelopment of complications after a short period ofLorenzo's oil use, the effectiveness of its use could not beassessed. Post Lorenzo's oil VLCFA level and brain MRIwill be repeated later after the child has fully recovered.

Discussion

X-ALD is a neurometabolic disorder that primarilyaffects the central nervous system, white matter and theadrenal cortex, which is caused by a defect in the ABCD1gene encoding the adrenoleukodystrophy protein (ALDP),

Figure 1 (A) Chest radiography showing multifocal increased opacity in both lungs. (B) High-resolution computedtomography scan of chest shows diffuse bilateral ground-glass opacities and smooth interstitial thickening with crazy-paving pattern in both lungs in posterior and lower lung zone predominantly.

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a transporter present in the peroxisomal membrane.3 ALDPdefects lead to accumulation of saturated VLCFA, such ashexacosanoic acid (C26:0), in the adrenal glands and nervoussystem, white matter and other tissues, and in plasma.4 Atpresent, only very limited disease-modifying treatments existto prevent the onset or slow the progression ofX-ALD. Several treatment options have been indicated inclinical trials, including Lorenzo's oil, antioxidants, allogenichaematopoietic stem cell transplantation and bone marrowtransplantation.5

Lorenzo's oil is a 4:1 mixture of glyceryl trioleate andglyceryl trierucate. Oral administration of this oil, combinedwith a moderate reduction in fat, normalises or significantlylowers the plasma levels of VLCFA in patients withX-ALD.6 It is available worldwide, however its clinicalefficacy or indications has not been established. Basu et al7

have analysed medical data of 116 male asymptomatic

paediatric patients who were administered Lorenzo's oilwhich proved actual improvements in health status as wellas MRI findings. Moser et al8 have reported a single armstudy to assess the effect of Lorenzo's oil and they concludedthat hexocosanoic acid reduction by Lorenzo's oil wasassociated with decreased risk of developing abnormalitiesin MRI. However, despite this reduction, some patients stillhave progressive characteristics of the disease. Althoughthe efficacy of Lorenzo's oil is still controversial, we optedfor supportive care and rehabilitation in our patient, as hewas already manifesting neurological impairment consistentwith the cerebral form of X-ALD.

Neurological impairment and associated swallowingdysfunction are significant risk factors for aspiration andexogenous LP.9 The histories of neurological impairmentand frequent choking during administration of Lorenzo'soil suggested LP in our case, but a history of oil ingestion

Figure 2 Cytologic findings of bronchoalveolar lavage fluid. Variable sized bubble-like vacuoles are observed withinthe foamy histiocytes (arrow, A-C). They were stained by oil red O stain and were bright red in color (C). Scattered ciliatedbronchial epithelial cells (arrowhead) were admixed with lipophages (B, C). Smeared lipoid material was also stained by oilred O stain (D). (A, Papanicolau stain, original magnification X400; B, Giemsa stain, original magnification X400; C, D,oil red O stain, original magnification X400).

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is often overlooked and exposure to the oil is often identifiedretrospectively after a diagnosis of LP is made.2

The clinical symptoms of LP can vary significantly amongindividuals, ranging from asymptomatic to life-threatening,according to the patient's age, amount and type of oilaspirated and duration of oil intake.2

A diagnosis of LP is initially made based on history ofoil exposure to oil and radiological findings.2 The best typeof imaging study to establish a diagnosis of LP is HRCT ofthe chest. The features of HRCT in children with LP areair-space consolidations and ground-glass attenuation,occasionally with a crazy-paving pattern, distributedbilaterally in the posterior and lower zones of the lungs,but none of these radiological features were specific to LP.1In addition, there is a discrepancy in severity between theradiological and clinical findings, i.e., patients are oftenasymptomatic despite extensive imaging findings.2

Bronchoscopy with BAL is a good diagnostic tool forLP. BAL fluid is macroscopically whitish or turbid withfat globules on the fluid surface, and specific staining ofrecovered lipid-laden alveolar macrophages is consistentwith a diagnosis of LP.10 The presence of extracellular oilydroplets is more specific to exogenous LP.2 In our case, adefinitive diagnosis was made by bronchoscopy andspecific staining of the BAL fluid with Oil Red O.

The natural history and outcome of LP are variable anddepend on the type, volume and distribution of oil aspirated.1There have been no studies defining the best therapeuticoption for LP. Treatment is primarily supportive andgenerally conservative, followed by treatment of thecomplications.1,2 However, there is a consensus that the keyobjective is to identify and discontinue exposure to theoffending agent, and that the best treatment for this diseaseis prevention.2

To our knowledge, this is the first case report in apaediatric patient with X-ALD who suffered LP afteradministration of Lorenzo's oil. Patients with X-ALD sufferfrom various neurological deficits, including swallowingdifficulty. In X-ALD patients with oromotor dysfunctions

are at high risk of LP while using Lorenzo's oil, wherephysicians should be aware and avoid if possible. Suchawareness can enable the early diagnosis and treatment andimprove the prognosis by discontinuing exposure to theoffending agent or to an appropriate treatment.

Competing Interests

All authors have no competing interests.

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