Fat embolism syndrome in Duchenne muscular dystrophy: an underdiagnosed complication

Introduction. Fat embolism syndrome (FES) is a rare but potentially life-threatening complication of long bone fractures, typically described in high-energy trauma. In patients with Duchenne Muscular Dystrophy (DMD), even minor trauma can result in FES, owing to long-standing osteoporosis and prolonged corticosteroid therapy, and the recognition can be challenging. 

Materials and methods. We report a case series of three non-ambulatory patients with DMD who developed fat embolism syndrome following traumatic events. Clinical presentation, diagnostic challenges, and management strategies were retrospectively analyzed. 

Results. All three patients presented with features consistent with FES, with diagnostic difficulties related to atypical mechanisms of injury and overlapping neuromuscular symptoms. Timely supportive management led to favorable clinical outcomes in all cases. 

Discussion. These cases illustrate the critical need to closely consider FES in DMD patients who experience unexplained respiratory or neurological decline following trauma. Conclusion: Prompt recognition and a multidisciplinary approach are critical to minimizing morbidity and supporting recovery.

Introduction

Duchenne Muscular Dystrophy (DMD) is a progressive X-linked neuromuscular disorder caused by mutations in the DMD gene leading to absent dystrophin protein ¹. The disease is characterized by progressive muscle weakness, loss of ambulation, respiratory insufficiency, cardiomyopathy, and premature death. Reduced mobility and long-term corticosteroid therapy contribute to the development of osteoporosis in the majority of patients ¹.

Fat embolism (FE) is a relatively common event following trauma or orthopedic procedures and often remains clinically silent. In contrast, Fat Embolism Syndrome (FES) is a rare but serious complication that occurs in up to 11% of patients with femoral fractures in the general population ². It is characterized by a classic triad of respiratory distress, neurological symptoms, and petechial rash ^2,3.

FES is primarily triggered by a sudden increase in intramedullary pressure, which causes bone marrow fat to enter the venous circulation, particularly through the distal metaphyseal vessels of the femur. The pathogenesis involves both mechanical obstruction and systemic inflammatory responses. Fat globules can occlude small blood vessels in organs such as the lungs, brain, and skin, leading to impaired circulation, ischemia, and subsequent organ dysfunction. In addition to mechanical blockage, the presence of fat in the bloodstream activates the complement system and stimulates the release of pro-inflammatory cytokines, triggering a systemic inflammatory response. This inflammation can cause endothelial injury and increased capillary permeability, further exacerbating tissue damage ³.

A recent systematic review identified only 23 reported DMD patients with FES in the literature, of whom seven died, highlighting the potential severity of this complication ².

Case presentation

Here we present a series of three male patients with DMD who developed FES symptoms following fractures of the femur. Details about the patients and clinical course are reported in Table I.

Patient #1

An 18-years-old non-ambulant male on daily steroids treatment since the age of four, with a history of delayed puberty, severe osteoporosis, and vertebral deformities. Following a car rear-end collision with no apparent injuries, the patient developed an acute anxious state accompanied by vertigo, vomiting and tachycardia, which rapidly progressed to cardiopulmonary shock and coma. He was initially admitted to a local Emergency Department (ED), where a femoral fracture was not suspected. Brain CT imaging was unremarkable, chest CT revealed bilateral cotton-like opacities, predominantly in the posterior-inferior regions, accompanied by interstitial congestion (Fig. 1-A). The patient was urgently transferred to our hospital in critical condition with respiratory and hemodynamic instability, requiring orotracheal intubation and ICU admission for advanced support due to acute left ventricular dysfunction. Although the rapid progression to multiorgan failure raised suspicion of acute myocarditis, cardiac MRI did not confirm this diagnosis. Given the patient’s history of a car accident, a lower limb X-ray was performed due to suspicion of fat embolism syndrome (FES), which confirmed the presence of a distal suprametaphyseal fracture of the right femur. The clinical suspicion was further supported by additional clinical and laboratory findings, including thrombocytopenia and anemia, which required red blood cell and plasma transfusions. Retinal hemorrhages were also noted, along with the gradual appearance of bilateral thalamocapsular lesions (Fig. 2). During a prolonged ICU stay, the patient was gradually weaned from mechanical ventilation. Neurological status progressively improved, ultimately resulting in full recovery of both motor and cognitive functions.

Patient #2

A 13-year-old non-ambulant male, on steroid therapy since the age of six and with no prior history of fractures, was referred to our ED following a fall from his wheelchair. He sustained distal metaphyseal fractures of both femurs and minor facial abrasions. A few hours after admission, the patient developed progressive respiratory worsening requiring non-invasive ventilation (NIV). Chest CT revealed bilateral areas of increased density with diffuse parenchymal consolidations (Fig. 1-B). Laboratory investigations showed moderate anemia and thrombocytopenia. The patient received supportive care, resulting in gradual clinical and radiological improvement, along with normalization of laboratory parameters. He was discharged in good general condition, although nocturnal NIV was continued as part of his long-term respiratory support regimen.

Patient #3

A 15-year-old non-ambulant boy with a history of steroid treatment since the age of seven was evaluated in our ED following simultaneous bilateral femoral fractures sustained from an accidental fall from his wheelchair. His medical history included mild restrictive respiratory disease, mild scoliosis, and reduced bone density, but no previous fractures. The patient was initially discharged with an indication for outpatient orthopedic follow-up. However, less than 48 hours later, he was re-admitted due to worsening respiratory function with tachypnea, low-grade fever, somnolence, tachycardia, and hypoxia. Laboratory exams detected hyponatremia. High-flow oxygen therapy, non-invasive ventilation, and intravenous diuretics were initiated. Due to persistent gas exchange impairment, helmet CPAP was started. Over the following days, as serum sodium levels normalized, the patient developed progressive anemia, requiring transfusion with packed red blood cells. A chest CT scan revealed bilateral, patchy, partially confluent pseudonodular consolidations, predominantly involving the posterior basal lung regions (Fig. 1-C). A diagnosis of fat embolism syndrome (FES) was made. The patient received supportive care and experienced a full clinical recovery, with normalization of both laboratory and radiological parameters within 6 days.

Discussion

Fat Embolism Syndrome (FES) remains a diagnostic challenge in patients with Duchenne Muscular Dystrophy (DMD), despite the presence of well-established risk factors such as long-term corticosteroid use, severe osteoporosis, and an increased susceptibility to long bone fractures. Prolonged corticosteroid therapy may play a dual role in this setting. While it delays loss of ambulation and preserves pulmonary function, it also promotes osteoporosis and bone fragility. Moreover, chronic steroid exposure may influence fat metabolism and vascular integrity, potentially contributing to the development of FES even in the absence of overt trauma. These mechanisms may further amplify the risk following minor fractures in DMD patients^4,5. Unlike most published DMD cases where diagnosis was delayed or post-mortem, our three patients survived following early multidisciplinary intervention. This series therefore offers valuable insight into the clinical variability, diagnostic challenges, particularly in individuals with pre-existing neuromuscular disability, where baseline respiratory and neurological impairment may obscure the early manifestations of FES. These cases also highlight the potential for full recovery in FES associated with DMD.

In Patient #1, the initial traumatic event was not thoroughly evaluated at the referring emergency department, leading to a missed diagnosis of a femoral fracture. Even after the fracture was identified upon admission to our centre, its clinical relevance was underestimated due to the patient’s critical condition and the presence of several atypical findings. Diagnostic efforts initially focused on alternative causes of multi-organ failure such as sepsis or acute myocarditis, further delaying the consideration of FES.

In Patient #2, although bilateral distal femoral fractures were promptly identified and chest CT revealed findings characteristic of fat embolism, the diagnosis of FES was not immediately recognized. The patient fulfilled several of Gurd’s criteria, including respiratory distress, hypoxemia with bilateral radiographic infiltrates, thrombocytopenia, and anemia.

Patient #3 had a more subacute presentation, with progressive respiratory decline and systemic symptoms emerging nearly two days after bilateral femoral fractures. The delayed symptom onset, coupled with nonspecific findings such as hyponatremia, contributed to initial diagnostic uncertainty. This case underscores the potential for delayed presentations of FES, even in the absence of classical early signs, and highlights the variable temporal profile of the syndrome in the DMD population.

Taken together, these cases emphasize the critical need for a high index of suspicion for FES in DMD patients presenting acute or progressive respiratory and/or neurological deterioration following even minor trauma where unnoticed fractures may occur. Clinical presentations may be atypical and evolve over time, with symptoms that overlap with more familiar DMD-related complications. Delayed diagnosis can result from this diagnostic ambiguity, but early recognition, prompt supportive care, and a multidisciplinary approach can significantly improve outcomes. Importantly, even in severe cases, substantial recovery is possible with appropriate medical management and rehabilitation. When FES is suspected, early diagnostic workup should include: chest CT to detect diffuse bilateral opacities with a patchy or ground-glass pattern, brain MRI (particularly T2-weighted and DWI sequences) to identify characteristic thalamocapsular or white matter lesions, and laboratory tests to monitor platelet count and hematocrit. Ophthalmologic evaluation may also reveal retinal hemorrhages or cotton-wool exudates supporting the diagnosis. Although fat globules can be demonstrated in blood, urine, or sputum samples using Sudan or Oil-Red-O staining, these tests are rarely used in clinical practice and find more common application in the context of forensic pathology for the grading of FES based on evaluation of fat embolism within pulmonary vessels⁶such as its aetiopathogenesis, its causal role in death determination, the impact of interfering factors (e.g. cardiopulmonary resuscitation or other medical procedures. Diagnosis remains primarily clinical, supported by imaging and laboratory findings. Currently, no officially recognized specific preventive measures for FES are available⁷. However, general strategies may reduce risk or allow earlier recognition, such as careful handling of fractures, timely orthopedic stabilization when indicated, monitoring of patients at high risk, and optimization of bone health through vitamin D, calcium, and, when appropriate, bisphosphonate therapy⁵. Awareness among clinicians is crucial, as early recognition and supportive care remain the only effective interventions to improve outcomes^7,8.

Take-home messages

• FES should always be suspected in DMD patients with acute respiratory or neurological deterioration following even minor trauma.
• Diagnosis relies on a combination of clinical suspicion and multimodal imaging rather than laboratory tests alone.
• Prompt supportive care can result in complete recovery, even in severe cases.
• Awareness among clinicians is essential to improve early recognition and outcomes.

Acknowledgements

This work was supported also by the Italian Ministry of Health with “Current Research” funds. TM, CM, DD and AD are members of the ERN EURO-NMD network.

Conflict of interest statement

The authors declare that they have no conflicts of interest to disclose.

Authors contributions

TM, CM, and DA contributed to the conception of the work, review of clinical data, case analysis, and drafting of the manuscript. All authors contributed to the final manuscript, critically reviewed its content, and approved the submitted version.

Ethical consideration

None.

History

Received: September 24, 2025

Accepted: November 17, 2025

Figures and tables

Figure 1. Each panel illustrates the characteristic Chest CT imaging pattern associated with Fat Embolism Syndrome in our case series. (A) Patient #1: diffuse, bilateral, symmetrical “cottony” alveolar opacities with posterior–inferior predominance and interstitial congestion. (B) Patient #2: bilateral areas of increased density, particularly in the right lung, with parenchymal consolidations in the right upper and lower lobes and smaller dependent consolidations in the left lung. (C) Patient #3: bilateral patchy, partially confluent pseudonodular consolidations, predominantly in the posterior basal regions.

Figure 2. Brain MRI of Patient #1. (A, B) MRI 9 days after trauma: bilateral T2 iperintense lesions located in the bilateral thalamo-capsular nucleus (A); areas of diffusion restriction in left thalamo-capsular nucleus (B), compatible with fat embolism. (C,D,E) MRI one month after the traumatic injury: reduction of previously evident T2 bilateral nucleo-thalamo-capsular signal alterations (C) and absence of restriction of diffusivity (D); multiple punctate hypointensities in magnetic susceptibility images (SWI) with diffuse subcortical and deep bihemispheric localization, bilateral thalamocapsular nucleus, and in the subtentorial area, suggestive of fat embolism (E,F).

Table I. Clinical characteristics of patients with DMD and fat embolism syndrome following femoral fracture.

	#1	#2	#3
Age	18 y	13 y	15 y
Genotype	del 10-11	del 49-50	del 49-50
Ambulatory	no	no	no
Ventilation	no	no	no
Type of fracture	right femoral distal suprametaphyseal cortical irregularity	bilateral femoral distal metaphyseal fracture	bilateral femoral distal metaphyseal fracture
Trauma mechanism	car accident	low energy accidental fall from wheelchair	low energy accidental fall from wheelchair
Time from trauma to FES symptoms	< 6h	24h	48h
Main symptoms	leg pain, neurological symptoms (vertigo, paralysis, confusion), vomiting; rapid cardio-respiratory deterioration	ARDS,	ARDS tachycardia, pyrexia, reduced vigilance
Chest CT	diffuse bilateral fluffy alveolar opacities (posterior/inferior) with interstitial congestion	bilateral ground-glass and consolidations, R > L, with centrilobular micronodules	fluffy bilateral nodular opacities, basal predominance
Fundoscopy findings	cottony exudates and retinal hemorrhages that	not done	not done
Neuroimaging	bilateral thalamocapsular T2-weighted hyperintensities	not done	not done
Inflammatory markers	elevated	elevated	elevated
Haematological changes	low platelet count	decreased haematocrit, and platelet count	decreased haematocrit and platelet count
FES treatment	intubation (4 wks), weaning with NIV/HFNC, inotropic/inodilator support, ceftriaxone, piperacillin-tazobactam, PEG, RBC/plasma transfusions	NIV, enoxaparin 4000 IU SC daily, ceftriaxone 1 g daily, iron supplement	Helmet CPAP, enoxaparin 3000 IU SC BID, cefazolin 2 g TID
Outcome	complete recovery (after long period of intensive rehab)	partial recovery (NIV was continued)	complete recovery (NIV not necessary)