INTRODUCTION

Fat embolism is defined as the presence of fat globules in the pulmonary or peripheral circulation, whereas fat embolism syndrome (FES) refers to the clinical manifestations that occur following an inciting event—most commonly orthopedic trauma—and typically present as a triad of respiratory distress, neurological disturbances, and a petechial rash [1]. Although up to 90% of trauma patients with major injuries may experience fat embolism, it is typically asymptomatic and usually only identified during postmortem analysis [2]. However, the reported rates of fat embolism progressing to FES vary widely, ranging from 0.25% to 33% [3]. This variability may stem from differences in diagnostic criteria and the potential for overdiagnosis in prospective studies compared to retrospective ones [4]. Established risk factors for developing FES include younger age, closed fractures, multiple fractures, and prolonged conservative management of long bone fractures [5]. The mortality rate for FES has been estimated at 11.8% [6], yet our understanding of the risk factors leading to severe FES or fatal outcomes remains limited.

FES is a multiorgan disease that can affect any microcirculatory system within the body [4]. Its hallmark symptoms are a triad of respiratory distress, neurological impairments, and a petechial rash [1]. The pulmonary circulation is most commonly affected, with up to 75% of patients experiencing respiratory difficulties [7]. Neurological abnormalities occur in up to 80% of patients and often follow pulmonary symptoms, although this is not always the case [8]. Although a petechial rash is part of the classic triad, it is seen in only 20% to 50% of cases [9]. Other commonly reported, though nonspecific, symptoms include tachycardia, hypotension, right heart strain, fever, retinopathy, renal involvement, and coagulopathy [8,9].

The diagnosis of FES is challenging due to the lack of standardized diagnostic criteria and relies primarily on clinical evaluation. Although laboratory tests and imaging studies can support the diagnosis, they are nonspecific and not definitive. Management of FES is predominantly supportive, as no targeted therapies have consistently proven effective. Preventive strategies—particularly early surgical fixation of the underlying bone fractures—remain the cornerstone of FES management to minimize its occurrence [1]. The purpose of this case report is to highlight the unpredictable nature of FES and to underscore the critical need for comprehensive investigations into predictive criteria for anticipating severe outcomes.

CASE REPORT

A 20-year-old man with no significant past medical history was admitted to the emergency department of a level I trauma center after a motorcycle accident. Upon arrival, he was alert and oriented, with a Glasgow Coma Scale (GCS) score of 15. He was hemodynamically stable, with a blood pressure of 110/86 mm Hg, a heart rate of 87 beats per minute, and was breathing spontaneously with a respiratory rate of 22 breaths per minute on room air, achieving an oxygen saturation of 99%. He was afebrile, and his initial lactate level was 1 mmol/L.

He was managed according to the local trauma protocol. An initial head computed tomography (CT) scan revealed a small subarachnoid hemorrhage in the right occipital region, with no other significant findings. Spine and pelvic CT identified a fracture of the right transverse process of the first coccygeal vertebra and a fracture of the superior ramus of the left pubic bone with dislocation of bony fragments. Chest, abdomen, and pelvis CT with contrast demonstrated only a small perivesical hematoma without other significant trauma. Long bone imaging revealed a closed fracture of the right femoral diaphysis, a grade II open fracture of the left tibia and fibula, a grade I open fracture of the right distal radius, and a closed fracture of the left distal radius. The Acute Physiology and Chronic Health Evaluation II (APACHE-II) and the Sequential Organ Failure Assessment (SOFA) scores were both 0 at admission, while the New Injury Severity Score (NISS) was 34, indicating severe trauma.

Following initial management with fluid resuscitation, analgesics, proton pump inhibitors, and tranexamic acid, the patient was transferred to the intensive care unit for further care while awaiting orthopedic evaluation regarding the timing of emergent surgery. The fractures were immobilized with casts immediately upon admission. Approximately 12 hours after hospital admission, his condition rapidly deteriorated; he became confused and lethargic, eventually becoming unresponsive with a GCS score of 3. He developed tachycardia, tachypnea, dyspnea, hypoxemia, cyanosis, and ultimately respiratory failure, necessitating urgent endotracheal intubation and mechanical ventilation. An immediate head CT revealed no new abnormalities. Both a CT brain perfusion scan and CT angiography of the head and neck showed no significant pathology. Physical examination demonstrated diffuse bilateral crackles. A subsequent CT pulmonary angiography revealed no perfusion deficits but identified new areas of ground-glass opacities and thickened interlobular septa bilaterally (Fig. 1).

A magnetic resonance imaging (MRI) scan of the head, obtained on the third day of admission, revealed numerous extensive, diffuse, punctate, and partially confluent lesions in both the supratentorial and infratentorial regions, including cortico-juxtacortical areas, periventricular white matter, bilateral basal ganglia, and the brainstem. Watershed zones of ischemia were noted bilaterally in the frontal and parieto-occipital regions, as well as in the deep periventricular white matter and the splenium of the corpus callosum. The MRI also displayed a “starfield pattern” on diffusion-weighted imaging and diffuse punctate microhemorrhages in the white matter on susceptibility-weighted imaging, findings most consistent with fat embolism (Fig. 2).

Following the establishment of the diagnosis, supportive care was continued in the intensive care unit per protocol. Over the subsequent days, a diffuse petechial rash developed, particularly in the bilateral axillae, anterior chest, abdominal wall, and neck (Fig. 3). The patient also developed a fever, and daily laboratory tests revealed worsening anemia, thrombocytopenia, hypocalcemia, and hypoalbuminemia. At this time, the patient met the clinical criteria for the diagnosis of FES. Despite all efforts, his condition continued to deteriorate, and he passed away one week after admission. Autopsy of the brain revealed diffuse punctate hemorrhages scattered throughout the white matter (Fig. 4). The autopsy report confirmed FES through microscopic examination of the affected organs using Sudan stain (Fig. 5).

Ethics statement

This study was conducted in compliance with the principles of the Declaration of Helsinki. Informed consent for publication of the research details and clinical images was obtained from the patient's next of kin.

DISCUSSION

Fat embolism occurs relatively frequently, with postmortem examinations revealing its presence in the vast majority of trauma patients, predominantly in the pulmonary circulation and less frequently in the cerebral circulation [2]. In contrast, FES is significantly rarer, with reported incidence rates varying widely depending on the population and study. A study by Bulger et al. [7] found an incidence of approximately 0.9% among patients with long bone fractures, with symptoms typically emerging within 24 to 48 hours post-injury, especially in cases involving lower extremity closed fractures. Another study reported an incidence of 0.17%, identifying femur fractures as the most common cause and noting that males, particularly those aged 10 to 40 years, were disproportionately affected with a relative risk of 5.7 [10]. Additionally, 98% of patients with femoral shaft fractures present with fat globules in their blood on admission, most concentrated in the venous circulation near the fracture site [11].

FES is believed to arise from a combination of mechanical disruption of fat within the bone marrow and a biochemical response involving the mobilization of fat stores. Trauma, such as long bone fractures, disrupts the fat within the marrow and tears blood vessels, allowing fat globules to enter the circulation. Although fat typically requires passage through a patent foramen ovale to enter the arterial circulation, neurological symptoms can occur without this anatomical variant, as fat may deform to navigate through capillaries or pass through arteriovenous shunts. Concurrently, trauma mobilizes fat from body stores, triggering an inflammatory response. Lipase breaks down the fat into free fatty acids, which are toxic to endothelial cells and lead to vasogenic edema and hemorrhage. This process releases proinflammatory cytokines that can result in acute respiratory distress syndrome, while aggregated fat in the blood may occlude vessels and contribute to thrombocytopenia and disseminated intravascular coagulation [1].

FES is most commonly associated with traumatic fractures, although it has also been observed following other traumatic events such as burns and soft tissue injuries. While FES has been documented across various patient populations, it predominantly affects men under the age of 40 years [6]. Our patient, a 20-year-old male, presented with the conventional risk factors for developing FES [5] and would therefore be considered high risk. Furthermore, a 2013 study suggests that the combination of polytrauma—defined by a NISS greater than 17—serum lactate levels exceeding 22 mmol/L, and transient hypoxemic episodes serves as a strong predictor for the development of FES [12]. Although our patient had a high NISS, his lactate level was only 1 mmol/L upon admission, and he experienced no transient hypoxemic episodes. A study by Tsai et al. [6], the first to analyze FES mortality by age distribution, identified age as a significant determinant of in-hospital mortality in trauma patients with FES, even after adjusting for clinical and demographic factors. The study found that patients over 65 years faced a markedly higher risk of fatal outcomes compared to younger individuals, despite the latter being most commonly affected by FES. This finding may be attributed to the generally poorer health status of elderly patients, who are more likely to present with concomitant comorbidities. Although data on risk factors for severe forms of FES and related mortality are limited, the fatal outcome in our young, previously healthy patient is unexpected based on the available evidence.

As noted earlier, the hallmark symptoms of FES comprise a triad of respiratory distress, neurological impairments, and a petechial rash [1]. Pulmonary symptoms typically emerge within 24 to 72 hours after trauma, although cases as early as 12 hours have been documented. Large emboli can cause acute cardiopulmonary collapse; however, FES more commonly presents gradually, beginning with dyspnea, tachypnea, and hypoxemia. Approximately half of all FES patients progress to respiratory failure, often requiring mechanical ventilation [13]. Neurological symptoms usually begin with confusion and agitation, resembling delirium, and can progress to include focal deficits such as hemiplegia, aphasia, seizures, and even coma [8,9]. The petechial rash commonly appears on the head, neck, thorax, axillae, subconjunctival spaces, and oral mucosa [9]. Although similar rashes may occur in sepsis and disseminated intravascular coagulation, the rash seen in FES is distinct in its anterior distribution and sparing of the back. This pattern likely results from fat droplets accumulating in the aortic arch and traveling through the carotid and subclavian arteries to nondependent areas in a supine patient [9].

Outcomes for individuals who develop FES are poor if the syndrome is not recognized early and aggressive supportive measures are not promptly implemented. When interventions occur early in the disease process, the prognosis tends to be favorable, with mortality rates now reported at under 10% [14]. In contrast, a meta-analysis by He et al. [15] in 2021 revealed an overall mortality rate of 30.2%, raising concerns that previous studies may have underestimated the associated risks. These discrepancies highlight the need for standardized diagnostic criteria and treatment protocols to achieve more consistent outcomes and a better understanding of FES’s impact on mortality.

A major challenge in diagnosing FES is the absence of a definitive benchmark test. The diagnosis is predominantly clinical, utilizing standard criteria established by Gurd, Schonfeld, and Lindeque [1]. Although these criteria aim to standardize diagnosis, they are derived from limited studies and have not been prospectively validated [1]. Currently, no laboratory tests are specific to FES; however, common findings may include anemia, thrombocytopenia, and elevated inflammatory markers [8]. Elevated serum lipase can lead to hypocalcemia, and albumin binding to free fatty acids can reduce free albumin levels. Although fat globules have been noted in blood, bronchoalveolar lavage fluid, and urine, their presence is not exclusive to FES [10]. Imaging studies provide valuable additional diagnostic information. Chest radiographs typically reveal bilateral diffuse or patchy ill-defined opacities, though these findings are nonspecific. High-resolution CT scans offer more specific findings, demonstrating patchy ground-glass opacities and consolidation with interlobular thickening—the so-called “crazy paving” pattern [16]. While brain CT may occasionally reveal diffuse edema with scattered hemorrhage, it is often unremarkable. In contrast, MRI is more sensitive; T2-weighted images typically display a “starfield pattern” characterized by multiple small, nonconfluent hyperintense lesions [17]. These lesions are also bright on diffusion-weighted imaging and dark on susceptibility-weighted sequences. Brain MRI findings consistently correlate with autopsy results, showing lesions in the periventricular, subcortical, and deep white matter, which contrasts with diffuse axonal injury that typically affects the gray–white matter junction [17]. Although the diagnosis is clinical, Shaikh et al. [5] suggest that all patients with suspected FES based on clinical criteria should undergo imaging studies, given the significant correlation between the major and minor clinical criteria and abnormal imaging findings.

The management of FES primarily involves supportive care aimed at maintaining oxygenation and ventilation, stabilizing hemodynamics, and providing fluid and blood product resuscitation. Over the past few decades, various targeted therapies—such as heparin, hypertonic glucose, increased fluid intake, aspirin, and corticosteroids—have been explored; however, none have demonstrated conclusive benefits, and routine prophylaxis is not recommended [8]. Given the absence of direct treatment options, prevention with early surgical fixation is crucial. In one study, late stabilization (within 48 hours as opposed to 24 hours) was associated with significantly more pulmonary complications, supporting the principle of early total care [18]. Nonetheless, some patients may benefit from damage control orthopedics followed by definitive treatment later. Pape et al. [19] recommend evaluating shock, coagulopathy, temperature, and soft tissue injury to guide treatment strategies. This method has been validated by several clinical studies, demonstrating improved outcomes when applied [20]. Balancing the prevention of FES with the patient’s physiological capacity for surgery remains essential.

FES presents a significant challenge in trauma care, particularly following orthopedic injuries. Although fat embolism occurs frequently, FES remains relatively rare and can lead to severe, multi-organ complications with high mortality rates. The diagnosis is complex, relying on clinical criteria in the absence of definitive tests, and the variability in reported incidence underscores the need for standardized protocols. Our case study highlights the unpredictable nature of FES, wherein even a young and otherwise healthy individual can succumb to the syndrome. Although our patient exhibited some risk factors for severe FES, he did not present with all established indicators. This observation underscores our limited understanding of the specific risk factors that contribute to severe presentations and fatal outcomes in FES. Future research should focus on defining and validating predictive criteria by investigating clinical factors such as the timing of initial symptoms, the presence of multiple fractures, and the severity of trauma. Additionally, the role of early vital sign changes—including tachypnea and oxygen desaturation—as well as imaging findings such as early ground-glass opacities, should be explored. Investigating these factors in combination with patient age, comorbidities, and injury mechanism may help establish more accurate risk stratification, leading to tailored management strategies and improved outcomes for high-risk patients. Furthermore, the current literature lacks consensus on whether emergent surgery or damage control strategies should be prioritized in managing such cases. This uncertainty highlights the need for further research to establish clearer guidelines, as the interplay of various risk factors can significantly influence clinical outcomes in patients with FES. Investigating preemptive treatment strategies, such as early stabilization of fractures and proactive respiratory support, may potentially prevent the progression of FES and should be explored in future studies to determine their efficacy in improving patient outcomes.

ARTICLE INFORMATION

Author contributions

Conceptualization: all authors; Investigation: all authors; Methodology: NB, SG; Project administration: NB, BJ; Visualization: NB, SG; Writing–original draft: NB, SG; Writing–review & editing: all authors. All authors read and approved the final manuscript.

Conflicts of interest

The authors have no conflicts of interest to declare.

Funding

The authors received no financial support for this study.

Data availability

Data sharing is not applicable as no new data were created or analyzed in this study.

Fig. 1.

The peribronchial regions in the posterobasal areas of both lungs display zones of increased parenchymal density consistent with consolidation, accompanied by accentuated interlobular septa (arrow).

Fig. 2.

Magnetic resonance imaging of the brain. (A–C) T2-weighted imaging. (A) The sagittal view, showing multiple hyperintense lesions, including involvement of the brainstem (red arrow) and confluent lesions in the parieto-occipital region (green arrow). (B) The transverse view, showing scattered punctate foci of cytotoxic edema forming a characteristic “starfield pattern” (green arrow). (C) The transverse view revealing periventricular lesions (green arrow). (D) A transverse view displaying numerous microhemorrhages throughout the white matter on T2 susceptibility-weighted imaging, creating a distinct “walnut kernel pattern.”

Fig. 3.

Characteristic petechiae in the axilla (arrow).

Fig. 4.

Transverse section of the brain postmortem revealing diffuse punctate hemorrhages scattered throughout the white matter (arrows).

Fig. 5.

Sudan-stained sections highlighting fat emboli in red (arrows) within specimens from (A) the brain (×100), (B) the lung (×400), and (C, D) the kidney (×100 and ×400, respectively).

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