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(Chest. 2005;127:2276-2281.)
© 2005 American College of Chest Physicians

Silicone Embolism Syndrome

A Case Report, Review of the Literature, and Comparison With Fat Embolism Syndrome*

Andreas Schmid, MD; Assaf Tzur, MD; Lidiya Leshko, MD and Bruce P. Krieger, MD, FCCP

* From the University of Miami, School of Medicine and Mount Sinai Medical Center, Miami Beach, FL.

Correspondence to: Bruce P. Krieger, MD, Professor of Medicine, University of Miami School of Medicine, Director of Intensive Care at Mount Sinai Medical Center, 4300 Alton Rd, Miami Beach, FL 33140; e-mail: bronchobruce{at}pol.net


   Abstract
TOP
 Abstract
Introduction
 Case Report
 Materials and Methods
 Results
 Discussion
 References
 
Liquid silicone is an inert material that is utilized for cosmetic procedures by physicians as well as illegally by nonmedical personnel. We present a case report and collated clinical findings of 32 other patients who were hospitalized after illegal silicone injections. Symptoms and signs of the "silicone syndrome" included dyspnea, fever, cough, hemoptysis, chest pain, hypoxia, alveolar hemorrhage, and altered consciousness. Bilateral patchy alveolar infiltrates were present on the chest radiographs, and silicone pulmonary emboli were detected in all the patients. The patients could be divided into two groups based on the initial presentation and clinical outcome. Twenty-seven patients in group 1 presented predominantly with respiratory symptoms, and 93% of patients were discharged home within 3 weeks. Six patients (group 2) presented with severe neurologic findings, and experienced rapid deterioration and 100% mortality. The clinical findings after silicone embolism are very similar to the published reports of fat embolism, including hypoxemia in 92% of patients with silicone embolism (patients with fat embolism, 56 to 96%), dyspnea in 88% of patients (patients with fat embolism, 56 to 75%), fever in 70% of patients (patients with fat embolism, 23 to 67%), alveolar hemorrhage in 64% of patients (patients with fat embolism, 66%), neurologic symptoms in 33% of patients (patients with fat embolism, 22 to 86%), petechiae in 18% of patients (patients with fat embolism, 20 to 50%), chest pain in 15% of patients (patients with fat embolism, 26%), and mortality in 24% of patients (patients with fat embolism, 5 to 20%). The similarities among the mode of injury to the lung, the clinical findings, and the high incidence of alveolar hemorrhage suggest a common pathogenesis of silicone and fat embolism syndromes. We discuss the possibility that the activation of the coagulation system may be important in the development of these clinical syndromes.

Key Words: alveolar hemorrhage • coagulation system • fat embolism • silicone embolism • subcutaneous silicone injection • thrombosis


   Introduction
TOP
 Abstract
 Introduction
Case Report
 Materials and Methods
 Results
 Discussion
 References
 
Liquid silicone (polydimethylsiloxane) is an inert material that has minimal tissue reaction, a high degree of thermal stability, a low surface tension, a lack of immunogenicity, and little or no change in physical property during aging.123 For these reasons, the injection of liquid silicone is frequently used for medical purposes, illegal breast augmentation, and other cosmetic procedures.

After a patient was hospitalized at our institution because of life-threatening pulmonary hemorrhage following illegal silicone injection, we collated all of the cases published in English of patients who had been hospitalized after illegal subcutaneous silicone injection with the aim of describing the common aspects of the silicone syndrome. We found a striking correlation between the clinical features following silicone injection and the features of fat embolism syndrome (FES).


   Case Report
TOP
 Abstract
 Introduction
 Case Report
Materials and Methods
 Results
 Discussion
 References
 
A 22-year-old transsexual man who was HIV-positive (CD4 count, 325 cells/µL), presented with cough, progressive severe dyspnea, chest tightness, and fever. The symptoms began 4 days prior to hospitalization, which was 1 day after the illegal subcutaneous injection of liquid silicone for bilateral breast augmentation. He had received smaller injections during the past 4 years without complications. The volume injected was approximately 700 mL, whereas previous infiltrations were < 100 mL. The physical examination findings were notable for tachycardia, tachypnea, a temperature of 99.7°F, and somnolence. Arterial blood gas measurements performed while the patient was breathing room air were as follows: pH, 7.40; PaCO2, 38 mm Hg; PaO2, 67 mm Hg; and arterial oxygen saturation, 92%. Bilateral, patchy, predominantly peripheral densities were seen on the chest radiograph (Fig 1 ). A CT scan of the chest demonstrated extensive peripheral airspace consolidations in both lungs (Fig 2 ). Fiberoptic bronchoscopy showed fresh blood in both major bronchi. During BAL of the left upper lobe with 100 mL of normal saline solution, the fluid return became progressively more hemorrhagic, indicating alveolar hemorrhage. Cytology showed 50% polymorphonuclear leukocytes, 44% macrophages, 4% lymphocytes, and 2% eosinophils. Silver staining of the BAL fluid had negative results as did stains and cultures for Mycobacterium, fungi, and bacteria. The transbronchial biopsy specimens from the left upper and left lower lobes showed foci of intra-alveolar hemorrhage with fibrin, focal thickening of alveolar walls due to inflammatory infiltrates, and prominent type II pneumocytes. In the interstitial capillaries, vacuolated globular deposits of silicone were found (Fig 3 ). Tests for other etiologies of alveolar hemorrhages, including antiglomerular basement membrane antibody (Ab), antinuclear Ab, antinuclear cytoplasmic Ab, and cryoglobulins, and drug screening for cocaine all had negative results. A pulmonary function test on hospital day 6 showed restrictive changes (total lung capacity, 4.4 L [52% predicted]) with increased diffusion capacity (184% predicted). IV methylprednisolone (initial dose, 120 mg/d; tapered to zero during the hospitalization) was administered, and the patient had a rapid clinical and radiographic improvement. He was discharged home without the need for further treatment on the sixth hospital day.



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  		Figure 1. Posteroanterior chest roentgenogram at hospital admission. A posteroanterior chest roentgenogram shows bilateral alveolar patchy infiltrates.

 


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  		Figure 2. Chest CT scan 1 day after hospital admission. A chest CT scan shows diffuse infiltrates involving mostly peripheral lung fields.

 


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  		Figure 3. Transbronchial biopsy specimen from the left lower lobe. The hematoxylin-eosin stain (original x40) of a transbronchial biopsy specimen from the left lower lobes shows foci of intraalveolar hemorrhage with fibrin, focal thickening of alveolar walls due to inflammatory infiltrates, and prominent type II pneumocytes. In the interstitial capillaries, vacuolated globular deposits (arrows) of silicone were found.

 
One week after hospital discharge, the patient presented with a thrombosis of the left internal jugular (LIJ) vein and pulmonary embolism, as documented by venous duplex imaging of the LIJ and a CT angiogram of the chest. The patient had never received a jugular or subclavian catheter, and screening for hypercoagulability showed a normal platelet count, prothrombin time, and international normalized ratio, and normal levels of factor V Leiden, protein S, protein C, and lupus anticoagulant. The results of a screening test for cardiolipin antibodies was borderline positive (IgG was low positive; IgM and IgA were negative). Anticoagulation therapy was initiated, and the patient was discharged home while receiving an oral coumadin regimen.


   Materials and Methods
TOP
 Abstract
 Introduction
 Case Report
 Materials and Methods
Results
 Discussion
 References
 
We searched MEDLINE and MEDSCAPE from 1965 until January 2004 using the key words "silicone," "embolism," and "subcutaneous injection," and found 11 articles published in English describing 32 patients who had been hospitalized hours to days after illegal subcutaneous silicone injections.23456789101112 We collated the clinical features of all 33 patients and divided them into two groups, based on the predominance of respiratory symptoms (group 1) and neurologic sequelae (group 2).


   Results
TOP
 Abstract
 Introduction
 Case Report
 Materials and Methods
 Results
Discussion
 References
 
There were 15 transsexual men and 18 women. The mean age was 31.4 years (age range, 21 to 58 years). The sites of silicone injection were breast (n = 14), trochanteric area (n = 13), vagina (n = 4), buttock (n = 1), and shoulder (n = 1). The reported amounts of injected silicone ranged between 50 and 1,000 mL. One patient developed symptoms after undergoing blunt trauma to an area that had been injected with silicone a few years previously,8 and another patient developed symptoms after the implantation of a breast prosthesis.3

The onset of clinical signs occurred within 24 h of injection in 72% of patients. Twenty-two percent of the patients presented within 24 to 48 h after silicone injections, and the remainder presented within 72 h. The major clinical findings included the following: hypoxemia, 92% of patients; dyspnea, 88% of patients; fever, 70% of patients; and alveolar hemorrhage, 64% of patients. Other findings are listed in Table 1 .


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  		Table 1. Distribution of Symptoms in Silicone Embolism Syndrome and FES*

 
The chest radiographs of all of the patients showed diffuse bilateral patchy alveolar infiltrates. The findings of ventilation-perfusion scans were reported for 12 patients. Eight scans showed a decrease in peripheral uptake without any segmental defects,79 and four scans were interpreted as having a "low probability" for pulmonary embolism,410 including the present report.

Alveolar hemorrhage was reported in 21 patients (64%). This was documented by showing an increasingly bloody fluid return during BAL in 12 patients, cytologic examination of the BAL fluid in 5 patients, or by review of the lung pathology in 3 patients. One patient with severe hemoptysis died without pathologic review.

The results of pulmonary function studies were reported in 19 cases, of which 17 (89%) showed restrictive changes. In 14 of the 21 patients with alveolar hemorrhage, pulmonary function testing was documented. The mean diffusing capacity of this group was 100.8% of predicted (range, 42 to 184% of predicted), and six patients (43%) had an increased diffusing capacity (> 110% of predicted).

The length of hospitalization was < 1 week in 9% of patients (n = 3), between 1 and 2 weeks in 56% of patients (n = 18), and > 2 weeks in 9% of patients (n = 3). Twenty-five percent of the patients (n = 8) died between 2 h and 30 days after hospitalization (mean, 6 days; median, 3 days). The condition of the patient with the silicone breast implants rapidly improved after explantation of the silicone prosthesis.3

Group Analysis
We found two distinct clinical patterns after injection of silicone. Twenty-seven patients (82%) [ie, group 1] presented with respiratory distress as the predominant feature,234678910 including the present report, whereas 6 patients (18% [group 2]) presented with severe neurologic changes and a rapid, uniformly fatal deterioration.45610

The typical findings of the silicone syndrome are represented in group 1, as follows: respiratory distress and hypoxia occurring within the first 72 h (67% within 24 h) after the injection of silicone. The major clinical findings at hospitalization were dyspnea, fever, chest pain, cough, hemoptysis, petechiae, and alveolar hemorrhage. The clinical course in this group was usually nonfatal with discharge of the patients from the hospital before 3 weeks in 93% (25 of 27 patients). Two patients died 12 and 30 days after hospitalization following severe pneumonia with septic shock12 and tuberculous pneumonia that afflicted the entire lung following steroid-induced reactivation of tuberculosis.6

The pulmonary pathologic and cytologic findings in group 1 were notable for signs of inflammation,8 which is similar to those for the patient in our reported case, who showed a neutrophil-predominant BAL fluid, as well as the presence of silicone globules in the alveolar space, interalveolar walls, pulmonary capillaries, and macrophages.267812

Besides the more common presentation of the silicone syndrome, we found six patients who presented with respiratory symptoms that were overshadowed by severe neurologic changes that manifested as altered consciousness, including coma. All of these patients developed symptoms during or several hours after their injections and deteriorated rapidly. Four patients died within 24 h and two patients died after 5 days of hospitalization.45611

Three of the six patients in group 2 had silicone injected into their vaginas, which contains a very dense venous plexus. In all six patients, there was an acute severe alteration of consciousness following the silicone injections, which suggested a possible cerebral embolism. In two patients, silicone emboli were detected outside the lung, including in the brain.45 There were no reports of patent foramen ovale in any of the patients that could explain the distribution of silicone in other organs other than the lung. Interestingly, acute inflammation in the lung was not noted in any group 2 patient, whereas 50% of the patients in group 1 had increased polymorphonuclear leukocytes in the BAL fluid.267812


   Discussion
TOP
 Abstract
 Introduction
 Case Report
 Materials and Methods
 Results
 Discussion
References
 
The clinical findings described in the patients with silicone embolisms are very similar to the presentation of patients with fat embolisms, as outlined in Table 1.131415161718192021 This suggests a common pathophysiology. Schonfeld et al22 defined FES by using a cumulative score that was composed of the presence of petechiae, chest radiographic changes, hypoxemia, fever, tachycardia, tachypnea, and confusion (Table 2 ). FES was defined by a score > 5. Using this classification, all of the patients with silicone embolisms in group 1 met the criteria for FES, with a mean Schonfeld score of 9 (median Schonfeld score, 8).789101112


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  		Table 2. The Criteria of Schonfeld et al22 for the Diagnosis of FES

 
Theories to explain the occurrence of respiratory failure after a fat embolism have focused on the obstruction of the lung capillaries131721232425 and on biochemical changes leading to lung toxicity.1617212326 The delay in developing symptoms in patients with both syndromes suggests that there is an intermediate substance responsible for the initiation of the pathologic changes. This substance is likely linked to the localization of the initial tissue damage or may be released as a consequence of the obstruction in the lung.

The fact that alveolar hemorrhage developed in a majority of patients with both silicone syndrome and FES, and that spontaneous LIJ vein thrombosis developed a week after the silicone embolism in the reported patient, suggests a role for the coagulation system in the two described syndromes. The coagulation system has been shown to be activated in experimental models of FES, and was a necessary component for the increase in alveolar-capillary permeability and edema in a bone marrow model.27 Oleic acid has been shown to induce acute lung injury,28 and bone marrow infusion has been shown to activate the coagulation system.27 The ingestion of silicone and fat by alveolar macrophages may provoke an inflammatory response by increasing vascular permeability, activating endothelial cells, inducing the accumulation of activated neutrophils (as shown in group 1 above), and modulating immunoregulatory responses in the lung.29 However, further experimental work will be necessary to investigate these possibilities.

We described a patient who developed alveolar hemorrhage and a spontaneous LIJ vein thrombosis following the subcutaneous injection of silicone. We collated information from 33 patients and noted that the features of silicone embolism syndrome were very similar to those of FES. The majority of patients with silicone embolisms developed pulmonary hemorrhages and survived. However, a subset of six patients (18%) presented with a fatal neurologic syndrome.


   Footnotes
 
Abbreviations: Ab = antibody; FES = fat embolism syndrome; LIJ = left internal jugular

Received for publication August 5, 2004. Accepted for publication January 25, 2005.


   References
TOP
 Abstract
 Introduction
 Case Report
 Materials and Methods
 Results
 Discussion
 References
 

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N. Engl. J. Med., January 12, 2006; 354(2): 211 - 212.
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