KR Cheon, HJ Cho, SS Kim, YJ Woo

Abstract

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

Background

Lipoid pneumonia (LP) is an uncommon disease caused by the presence and accumulation of lipid compounds in the pulmonary tract and alveoli.^1,2 The clinical symptoms are non-specific, such as dyspnoea and/or cough and variable, ranging from asymptomatic to as severe as life-threatening.¹ It can be classified into endogenous and exogenous 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 to treatment with Lorenzo's oil in a patient with childhood cerebral form X-linked adrenoleukodystrophy (X-ALD). To our knowledge, this is the first case report demonstrating an association between Lorenzo's oil therapy and LP in a paediatric patient with X-ALD.

Case Presentation

A 6-year-old boy was admitted to hospital presenting with a 1-week history of cough and sputum. At the age of 5 years, he was diagnosed with the cerebral form of X-ALD with rapid regression and motor weakness. On admission, he could not walk or sit by himself however required per oral feeding without any gastric tube. Genetic analysis confirmed the diagnosis by identifying an ABCD1 gene mutation. At the time of the genetic analysis, increased levels of very long-chain fatty acids (VLCFAs) were also detected (C26:0 = 4.74 mmol/L (normal <1.30 mmol/L) and C26:0/C22:0 = 0.072 (normal <0.023)). Brain magnetic resonance imaging (MRI) revealed bilateral hyperintense lesions involving the frontal and occipital periventricular white matter, internal capsule, genu and splenium of the corpus callosum and corticospital tract. In addition, linear and nodular enhancements in the corpus callosum and internal capsule were also noted. These findings were compatible with ALD. As there is no disease-modifying treatment to prevent the onset or slow the progression of this disease, the parents of the patient were informed of several treatment options including haematopoietic stem cell transplantation. 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 daily for the last 3 months, together with supportive care and rehabilitation. 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 auscultated bilaterally without any signs of chest retraction or tachypnoea and the saturation of O₂ was 95~98% in room air. Chest radiography showed multifocally increased opacity in both lung fields (Figure 1A). High-resolution computed tomography (HRCT) of the chest showed diffuse bilateral ground glass opacity and smooth interstitial thickening with a crazy-paving pattern in both lungs, predominantly in the posterior and lower lung zones. These findings were compatible with LP (Figure 1B).

The patient underwent diagnostic bronchoscopy with bronchoalveolar lavage (BAL). The bronchoscopic findings indicated no endobronchial lesions, but whitish secretions were drained from the posterior segmental bronchi of the right upper lobe and superior segmental bronchi of the right lower lobe and BAL was performed from this lesion. Bacterial, mycobacterial and fungal analyses of the BAL fluid were negative, and the BAL fluid was also negative for malignant cells.

The BAL fluid showed a milky whitish appearance. Oil red O staining demonstrated numerous lipid-laden macrophages (Figure 2). The patient was confirmed to have LP and was hospitalised for 10 days with supportive care. His symptoms gradually improved and after the occurence of LP, he discontinued taking Lorenzo's oil. Due to the early development of complications after a short period of Lorenzo's oil use, the effectiveness of its use could not be assessed. Post Lorenzo's oil VLCFA level and brain MRI will be repeated later after the child has fully recovered.

Figure 1 (A) Chest radiography showing multifocal increased opacity in both lungs. (B) High-resolution computed tomography 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.

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

Discussion

X-ALD is a neurometabolic disorder that primarily affects the central nervous system, white matter and the adrenal cortex, which is caused by a defect in the ABCD1 gene encoding the adrenoleukodystrophy protein (ALDP), a transporter present in the peroxisomal membrane.³ ALDP defects lead to accumulation of saturated VLCFA, such as hexacosanoic acid (C26:0), in the adrenal glands and nervous system, white matter and other tissues, and in plasma.⁴ At present, only very limited disease-modifying treatments exist to prevent the onset or slow the progression of X-ALD. Several treatment options have been indicated in clinical trials, including Lorenzo's oil, antioxidants, allogenic haematopoietic stem cell transplantation and bone marrow transplantation.⁵

Lorenzo's oil is a 4:1 mixture of glyceryl trioleate and glyceryl trierucate. Oral administration of this oil, combined with a moderate reduction in fat, normalises or significantly lowers the plasma levels of VLCFA in patients with X-ALD.⁶ It is available worldwide, however its clinical efficacy or indications has not been established. Basu et al⁷ have analysed medical data of 116 male asymptomatic paediatric patients who were administered Lorenzo's oil which proved actual improvements in health status as well as MRI findings. Moser et al⁸ have reported a single arm study to assess the effect of Lorenzo's oil and they concluded that hexocosanoic acid reduction by Lorenzo's oil was associated with decreased risk of developing abnormalities in MRI. However, despite this reduction, some patients still have progressive characteristics of the disease. Although the efficacy of Lorenzo's oil is still controversial, we opted for supportive care and rehabilitation in our patient, as he was already manifesting neurological impairment consistent with the cerebral form of X-ALD.

Neurological impairment and associated swallowing dysfunction are significant risk factors for aspiration and exogenous LP.⁹ The histories of neurological impairment and frequent choking during administration of Lorenzo's oil suggested LP in our case, but a history of oil ingestion is often overlooked and exposure to the oil is often identified retrospectively after a diagnosis of LP is made.²

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

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

Bronchoscopy with BAL is a good diagnostic tool for LP. BAL fluid is macroscopically whitish or turbid with fat globules on the fluid surface, and specific staining of recovered lipid-laden alveolar macrophages is consistent with a diagnosis of LP.¹⁰ The presence of extracellular oily droplets is more specific to exogenous LP.² In our case, a definitive diagnosis was made by bronchoscopy and specific staining of the BAL fluid with Oil Red O.

The natural history and outcome of LP are variable and depend on the type, volume and distribution of oil aspirated.¹ There have been no studies defining the best therapeutic option for LP. Treatment is primarily supportive and generally conservative, followed by treatment of the complications.^1,2 However, there is a consensus that the key objective is to identify and discontinue exposure to the offending agent, and that the best treatment for this disease is prevention.²

To our knowledge, this is the first case report in a paediatric patient with X-ALD who suffered LP after administration of Lorenzo's oil. Patients with X-ALD suffer from various neurological deficits, including swallowing difficulty. In X-ALD patients with oromotor dysfunctions are at high risk of LP while using Lorenzo's oil, where physicians should be aware and avoid if possible. Such awareness can enable the early diagnosis and treatment and improve the prognosis by discontinuing exposure to the offending agent or to an appropriate treatment.

Competing Interests

All authors have no competing interests.

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