Accepted Manuscript Rewriting history: fever of unknown origin Aimee K. Zaas, MD, Section Editor, Jenna R. Bordelon, BS, Syeda U. Abbas, MD, Arsalan Q. Shabbir, MD, Phd, Andrew L. Ross, MD PII:
S0002-9343(15)00437-4
DOI:
10.1016/j.amjmed.2015.05.006
Reference:
AJM 12990
To appear in:
The American Journal of Medicine
Received Date: 16 December 2014 Revised Date:
6 May 2015
Accepted Date: 6 May 2015
Please cite this article as: Zaas AK, Bordelon JR, Abbas SU, Shabbir AQ, Ross AL, Rewriting history: fever of unknown origin, The American Journal of Medicine (2015), doi: 10.1016/j.amjmed.2015.05.006. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT 14-1813BordelonCHS, Page 1 of 7 Rewriting history: fever of unknown origin Jenna R. Bordelon B.S.1, 2, Syeda U. Abbas M.D.2, Arsalan Q. Shabbir M.D., Ph.D.1, Andrew L.
RI PT
Ross M.D.1
1. University of Miami Department of Dermatology and Cutaneous Surgery, Miami, Florida, USA.
SC
2. University of Miami Department of Internal Medicine, Miami, Florida, USA.
Corresponding Author
M AN U
Andrew L. Ross M.D. [email protected] 1600 NW 10th Ave Room 2023 Miami FL 33136
TE D
(847)772-0731
Funding/Support: This study was performed without financial funding or support.
EP
Financial Disclosures: None listed
AC C
All of the authors had access to the data and participated in the preparation of the manuscript.
Article Type: Diagnostic Dilemma
Key words: fever of unknown origin, silicone, granuloma
Running Title: Silicone fever
Word Count (manuscript text plus references): 1,455
ACCEPTED MANUSCRIPT 14-1813BordelonCHS, Page 2 of 7 Diagnostic Dilemma
Rewriting history: fever of unknown origin
RI PT
Aimee K. Zaas, MD, Section Editor
Jenna R. Bordelon, BS,a,b Syeda U. Abbas, MD,b Arsalan Q. Shabbir, MD, Phda Andrew L.
SC
Ross, MDa
Departments of aDermatology and Cutaneous Surgery and bInternal Medicine, Miller School of
M AN U
Medicine, University of Miami, Miami, FL.
Requests for reprints should be addressed to Andrew L. Ross, MD, 1600 NW 10th Avenue, Room 2023, Miami, FL, 33136.
PRESENTATION
TE D
E-mail address: [email protected]
EP
Sometimes, several attempts at an accurate history are necessary before questioning elicits crucial information. The diagnosis for a 34-year-old woman with type 1 diabetes remained elusive until she provided a missing detail. She was transferred from an outside hospital, where
AC C
she originally presented with a 5-month history of quotidian fevers up to 104°F (40°C). These were accompanied by lethargy, malaise, and significant weight loss. A review of systems was otherwise negative. The patient, an accountant, had no significant past surgical or family history. She was maintained on insulin and denied any use of alcohol, tobacco, or illicit substances. Initial laboratory findings were significant for an erythrocyte sedimentation rate of 140 mm/hr and severe anemia of chronic disease (hemoglobin, 8.3 g/dL). Empiric antibiotic treatment produced no response. The patient continued to be febrile with no clear infectious source. Specialists in rheumatology and infectious disease were
ACCEPTED MANUSCRIPT 14-1813BordelonCHS, Page 3 of 7 consulted, and extensive specialty-based studies were performed. Aside from a mildly elevated smooth muscle antibody titer (1:160), the workup remained negative for rheumatologic and infectious causes. Computed tomography of the chest, abdomen, and pelvis was significant for hepatomegaly plus enlargement of retroperitoneal and inguinal lymph nodes. Further evaluation
RI PT
included a lymph node biopsy, which showed reactive hyperplasia. Liver and bone marrow biopsy results were nondiagnostic.
ASSESSMENT
SC
The patient was again transferred, this time to our tertiary referral center for further evaluation of a fever of unknown origin. Upon arrival, her vital signs were stable except for a temperature of
M AN U
104°F (40°C). Physical examination was significant for hyperpigmented, indurated plaques on the bilateral external thighs. The plaques were exquisitely warm and tender (Figure 1). Significant bilateral inguinal lymphadenopathy was also present.
Pertinent laboratory studies revealed anemia (hemoglobin, 8.1 g/dl), a lactate dehydrogenase level of 558 IU/L, and an erythrocyte sedimentation rate of >140 mm/hr. Further inquiry did not uncover any history of recent travel, new medications, exposure to exotic
TE D
animals, insect bites, or ingestion of raw meat or unpasteurized dairy products. Additional evaluation of her cutaneous lesions included magnetic resonance imaging of the pelvis; results were significant for a heterogeneous appearance within the soft tissues of the buttocks and numerous areas of signal void (Figure 2). A tagged white blood cell scan showed no abscesses.
EP
The etiology of the patient’s symptoms remained unclear, and she was questioned again about her history. She acknowledged that 2 years earlier, an unlicensed practitioner had
AC C
administered silicone injections into her thighs on a single occasion to alter their shape. Consequently, a systemic inflammatory reaction due to silicone granulomas was suspected. The dermatology department was consulted, and the plaque was biopsied. A tissue culture was negative for fungi and mycobacteria. Histopathology of the biopsy sample disclosed granulomatous inflammation with a Swiss-cheese-like vacuolar pattern indicative of silicone granulomas (Figure 3).
DIAGNOSIS
ACCEPTED MANUSCRIPT 14-1813BordelonCHS, Page 4 of 7 Our patient presented with a prolonged fever of unknown origin and received the recently established diagnosis of autoimmune/inflammatory syndrome induced by adjuvants; the disorder was induced by silicone administration. Autoimmune/inflammatory syndrome induced by adjuvants encompasses several adjuvant-induced conditions that manifest with symptoms such as
RI PT
arthralgia, chronic fatigue, cognitive impairment, fever, malaise, myalgia, and myositis.1 Aluminum, pristane, and silicone are examples of frequent culprits, as are vaccines and
infectious agents. While exposure to these possible precipitants can be quite common, induction of autoimmune/inflammatory syndrome is surprisingly rare.1
SC
Proposed major criteria for identification of this new clinical entity include exposure to an external adjuvant, infection, or vaccine with subsequent development of clinical
M AN U
manifestations; improvement after removal of the inciting agent; and biopsy results typical for the suspected agent. Minor criteria include the presence of antibodies directed at the suspected adjuvant; identification of specific human leukocyte antigen genotypes in the patient; and development of a defined autoimmune disease (eg, multiple sclerosis or systemic sclerosis).1 A number of well-established complications have been tied to the use of liquid injectable silicone to fill soft tissue. Migration of the silicone from the injection site and soft tissue
TE D
inflammation with granuloma formation are commonly reported.2 More serious complications are silicone embolism, pneumonitis, hepatitis, and death.3-6 While injectable medical grade liquid silicone has been approved by the United States Food and Drug Administration for use in the treatment of retinal detachment, it is not approved as a dermal filler. Yet, substantial off-label use
EP
occurs. It has been suggested that a serial microdroplet puncture technique for administration of highly purified liquid injectable silicone can significantly minimize the risk associated with cosmetic procedures involving the material.7,8 More concerning, as in our patient’s case, is the
AC C
illicit provision of nonmedical grade liquid injectable silicone by unlicensed practitioners.9 The complications caused by employing nonmedical grade liquid injectable silicone as a dermal filler are well established and reviewed in depth elsewhere.10 In the workup for fever of unknown origin, clues gleaned from history, physical
examination, and basic laboratory evaluations can often be misleading.11 However, in this patient’s situation, the history of silicone injections at the site of these plaques was not only tantamount to making the diagnosis but also the missing element that perpetuated an unnecessary workup. Diagnostic inquiries in patients with fever of unknown origin are frequently directed
ACCEPTED MANUSCRIPT 14-1813BordelonCHS, Page 5 of 7 toward uncovering a rheumatologic illness, an infectious disease, or a malignancy.12 In the pursuit of each of these entities as a potential cause of this patient’s fever, the final diagnosis was delayed. Therefore, clinicians should be careful to include etiologies like
adjuvants in the differential for fever of unknown origin.
MANAGEMENT
RI PT
inflammatory/granulomatous reactions and autoimmune/inflammatory syndrome induced by
Upon diagnosis, the patient began treatment with methylprednisolone, and her fever and malaise
SC
resolved. She was eventually transitioned from systemic corticosteroids to minocycline.
Although her fever and malaise had not recurred at her 8-month follow-up visit, she did report
M AN U
discomfort localized to the indurated plaques.
Management of autoimmune/inflammatory syndrome induced by adjuvants is adjuvantspecific and should be tailored to each patient’s particular manifestations.1 Although data are limited on treating silicone-induced systemic autoimmune/inflammatory responses, reports have shown that complete surgical excision can ameliorate symptoms.13,14 Other treatment options that have met with variable success include systemic steroids, minocycline, etanercept, allopurinol,
TE D
and pentoxifylline.15-19
It is important to note that silicone-induced systemic and granulomatous reactions can develop years after the injection. As such, patients may not immediately divulge a history of silicone augmentation to their providers; they may not realize that a past exposure is relevant.
EP
For that reason, direct questioning about exposure to adjuvants, such as liquid injectable silicone, should be part of the workup for a patient with fever of unknown origin. This careful practice can
AC C
give insightful clues into the source of fever before extensive workups are conducted and empirical treatment is administered. Lastly, practitioners should advise patients interested in liquid injectable silicone filler to avoid unlicensed practitioners and nonmedical grade products.
References
1. Perricone C, Colafrancesco S, Mazor RD, Soriano A, Agmon-Levin N, Shoenfeld Y. Autoimmune/inflammatory syndrome induced by adjuvants (ASIA) 2013: unveiling the pathogenic, clinical, and diagnostic aspects. J Autoimmun. 2013;47:1-16.
ACCEPTED MANUSCRIPT 14-1813BordelonCHS, Page 6 of 7 2. Altmeyer MD, Anderson LL, Wang AR. Silicone migration and granuloma formation. J Cosmet Dermatol. 2009;8:92-97.
3. Schmid A, Tzur A, Leshko L, Krieger BP. Silicone embolism syndrome: a case report, review of the literature, and comparison with fat embolism syndrome. Chest. 2005;127:2276-2281.
RI PT
4. Price EA, Schueler H, Perper JA. Massive systemic silicone embolism: a case report and review of literature. Am J Forensic Med Pathol. 2006;27:97-102.
5. Ellenbogen R, Rubin L. Injectable fluid silicone therapy. Human morbidity and mortality. JAMA. 1975;234:308-309.
SC
6. Restrepo CS, Artunduaga M, Carrillo JA, et al. Silicone pulmonary embolism: Report of 10 cases and review of the literature. Silicone pulmonary embolism: report of 10 cases and review of the literature. J Comput Assist Tomogr. 2009;33:233-237.
2):1530-1541.
M AN U
7. Duffy DM. Liquid silicone for soft tissue augmentation. Dermatol Surg. 2005;31(11 Pt 8. Orentreich DS. Liquid injectable silicone: Techniques for soft tissue augmentation. Clin Plast Surg. 2000;27:595-612.
9. Ellis LZ, Cohen JL, High W. Granulomatous reaction to silicone injection. J Clin Aesthet Dermatol. 2012;5:44-47.
TE D
10. Styperek A, Bayers S, Beer M, Beer K. Nonmedical-grade injections of permanent fillers: medical and medicolegal considerations. J Clin Aesthet Dermatol. 2013;6:22-29.
11. Bleeker-Rovers CP, Vos FJ, de Kleijn EM, et al. A prospective multicenter study on fever of unknown origin: the yield of a structured diagnostic protocol. Medicine (Baltimore).
EP
2007;86:26-38.
12. Zenone T. Fever of unknown origin in adults: Evaluation of 144 cases in a non-university hospital. Scand J Infect Dis. 2006;38:632-638.
AC C
13. Copeland M, Kressel A, Spiera H, Hermann G, Bleiweiss IJ. Systemic inflammatory disorder related to fibrous breast capsules after silicone implant removal. Plast Reconstr
Surg. 1993;92:1179-1181.
14. Kappel RM, Pruijn GJ. The monobloc hydrogel breast implant, experiences and ideas. Eur J Plast Surg. 2012;35:229-233.
15. Genovese MC. Fever, rash, and arthritis in a woman with silicone gel breast implants. West J Med. 1997;167:149-158.
ACCEPTED MANUSCRIPT 14-1813BordelonCHS, Page 7 of 7 16. Arin MJ, Bäte J, Krieg T, Hunzelmann N. Silicone granuloma of the face treated with minocycline. J Am Acad Dermatol. 2005;52(2 Suppl 1):53-56.
17. Desai AM, Browning J, Rosen T. Etanercept therapy for silicone granuloma. J Drugs Dermatol. 2006;5:894-896.
RI PT
18. Redondo P, Del Olmo J, Alberola I. In situ and distant foreign body granulomas caused by silicone. Treatment with allopurinol. Br J Dermatol. 2005;152:1064-1065.
19. Teuber SS, Reilly DA, Howell L, Oide C, Gershwin ME. Severe migratory granulomatous
SC
reactions to silicone gel in 3 patients. J Rheumatol. 1999;26:699-704.
Figure 1. The patient had a hyperpigmented, indurated, warm, exquisitely tender plaque on the
M AN U
external right buttock and the posteriolateral thigh.
Figure 2. T1-weighted magnetic resonance imaging of the pelvis with contrast enhancement and fat suppression demonstrated a heterogeneous appearance within the soft tissues surrounding the buttocks. This was representative of an intense inflammatory process. Numerous areas of signal void were consistent with silicone deposits.
TE D
Figure 3. A biopsy sample of the indurated plaque was stained with hematoxylin and eosin. A, A granulomatous inflammatory infiltrate was seen in the reticular dermis, bar = 200 µm. B, Clear, nonbirefringent vacuoles were visualized at the inferior portion of the specimen consistent with
EP
silicone, bar = 200 µm. C, Magnification highlighted vacuoles with a Swiss-cheese-like
AC C
appearance, 50 µm.
AC C
EP
TE D
M AN U
SC
RI PT
ACCEPTED MANUSCRIPT
AC C
EP
TE D
M AN U
SC
RI PT
ACCEPTED MANUSCRIPT
AC C
EP
TE D
M AN U
SC
RI PT
ACCEPTED MANUSCRIPT
S0002-9343(15)00437-4
DOI:
10.1016/j.amjmed.2015.05.006
Reference:
AJM 12990
To appear in:
The American Journal of Medicine
Received Date: 16 December 2014 Revised Date:
6 May 2015
Accepted Date: 6 May 2015
Please cite this article as: Zaas AK, Bordelon JR, Abbas SU, Shabbir AQ, Ross AL, Rewriting history: fever of unknown origin, The American Journal of Medicine (2015), doi: 10.1016/j.amjmed.2015.05.006. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT 14-1813BordelonCHS, Page 1 of 7 Rewriting history: fever of unknown origin Jenna R. Bordelon B.S.1, 2, Syeda U. Abbas M.D.2, Arsalan Q. Shabbir M.D., Ph.D.1, Andrew L.
RI PT
Ross M.D.1
1. University of Miami Department of Dermatology and Cutaneous Surgery, Miami, Florida, USA.
SC
2. University of Miami Department of Internal Medicine, Miami, Florida, USA.
Corresponding Author
M AN U
Andrew L. Ross M.D. [email protected] 1600 NW 10th Ave Room 2023 Miami FL 33136
TE D
(847)772-0731
Funding/Support: This study was performed without financial funding or support.
EP
Financial Disclosures: None listed
AC C
All of the authors had access to the data and participated in the preparation of the manuscript.
Article Type: Diagnostic Dilemma
Key words: fever of unknown origin, silicone, granuloma
Running Title: Silicone fever
Word Count (manuscript text plus references): 1,455
ACCEPTED MANUSCRIPT 14-1813BordelonCHS, Page 2 of 7 Diagnostic Dilemma
Rewriting history: fever of unknown origin
RI PT
Aimee K. Zaas, MD, Section Editor
Jenna R. Bordelon, BS,a,b Syeda U. Abbas, MD,b Arsalan Q. Shabbir, MD, Phda Andrew L.
SC
Ross, MDa
Departments of aDermatology and Cutaneous Surgery and bInternal Medicine, Miller School of
M AN U
Medicine, University of Miami, Miami, FL.
Requests for reprints should be addressed to Andrew L. Ross, MD, 1600 NW 10th Avenue, Room 2023, Miami, FL, 33136.
PRESENTATION
TE D
E-mail address: [email protected]
EP
Sometimes, several attempts at an accurate history are necessary before questioning elicits crucial information. The diagnosis for a 34-year-old woman with type 1 diabetes remained elusive until she provided a missing detail. She was transferred from an outside hospital, where
AC C
she originally presented with a 5-month history of quotidian fevers up to 104°F (40°C). These were accompanied by lethargy, malaise, and significant weight loss. A review of systems was otherwise negative. The patient, an accountant, had no significant past surgical or family history. She was maintained on insulin and denied any use of alcohol, tobacco, or illicit substances. Initial laboratory findings were significant for an erythrocyte sedimentation rate of 140 mm/hr and severe anemia of chronic disease (hemoglobin, 8.3 g/dL). Empiric antibiotic treatment produced no response. The patient continued to be febrile with no clear infectious source. Specialists in rheumatology and infectious disease were
ACCEPTED MANUSCRIPT 14-1813BordelonCHS, Page 3 of 7 consulted, and extensive specialty-based studies were performed. Aside from a mildly elevated smooth muscle antibody titer (1:160), the workup remained negative for rheumatologic and infectious causes. Computed tomography of the chest, abdomen, and pelvis was significant for hepatomegaly plus enlargement of retroperitoneal and inguinal lymph nodes. Further evaluation
RI PT
included a lymph node biopsy, which showed reactive hyperplasia. Liver and bone marrow biopsy results were nondiagnostic.
ASSESSMENT
SC
The patient was again transferred, this time to our tertiary referral center for further evaluation of a fever of unknown origin. Upon arrival, her vital signs were stable except for a temperature of
M AN U
104°F (40°C). Physical examination was significant for hyperpigmented, indurated plaques on the bilateral external thighs. The plaques were exquisitely warm and tender (Figure 1). Significant bilateral inguinal lymphadenopathy was also present.
Pertinent laboratory studies revealed anemia (hemoglobin, 8.1 g/dl), a lactate dehydrogenase level of 558 IU/L, and an erythrocyte sedimentation rate of >140 mm/hr. Further inquiry did not uncover any history of recent travel, new medications, exposure to exotic
TE D
animals, insect bites, or ingestion of raw meat or unpasteurized dairy products. Additional evaluation of her cutaneous lesions included magnetic resonance imaging of the pelvis; results were significant for a heterogeneous appearance within the soft tissues of the buttocks and numerous areas of signal void (Figure 2). A tagged white blood cell scan showed no abscesses.
EP
The etiology of the patient’s symptoms remained unclear, and she was questioned again about her history. She acknowledged that 2 years earlier, an unlicensed practitioner had
AC C
administered silicone injections into her thighs on a single occasion to alter their shape. Consequently, a systemic inflammatory reaction due to silicone granulomas was suspected. The dermatology department was consulted, and the plaque was biopsied. A tissue culture was negative for fungi and mycobacteria. Histopathology of the biopsy sample disclosed granulomatous inflammation with a Swiss-cheese-like vacuolar pattern indicative of silicone granulomas (Figure 3).
DIAGNOSIS
ACCEPTED MANUSCRIPT 14-1813BordelonCHS, Page 4 of 7 Our patient presented with a prolonged fever of unknown origin and received the recently established diagnosis of autoimmune/inflammatory syndrome induced by adjuvants; the disorder was induced by silicone administration. Autoimmune/inflammatory syndrome induced by adjuvants encompasses several adjuvant-induced conditions that manifest with symptoms such as
RI PT
arthralgia, chronic fatigue, cognitive impairment, fever, malaise, myalgia, and myositis.1 Aluminum, pristane, and silicone are examples of frequent culprits, as are vaccines and
infectious agents. While exposure to these possible precipitants can be quite common, induction of autoimmune/inflammatory syndrome is surprisingly rare.1
SC
Proposed major criteria for identification of this new clinical entity include exposure to an external adjuvant, infection, or vaccine with subsequent development of clinical
M AN U
manifestations; improvement after removal of the inciting agent; and biopsy results typical for the suspected agent. Minor criteria include the presence of antibodies directed at the suspected adjuvant; identification of specific human leukocyte antigen genotypes in the patient; and development of a defined autoimmune disease (eg, multiple sclerosis or systemic sclerosis).1 A number of well-established complications have been tied to the use of liquid injectable silicone to fill soft tissue. Migration of the silicone from the injection site and soft tissue
TE D
inflammation with granuloma formation are commonly reported.2 More serious complications are silicone embolism, pneumonitis, hepatitis, and death.3-6 While injectable medical grade liquid silicone has been approved by the United States Food and Drug Administration for use in the treatment of retinal detachment, it is not approved as a dermal filler. Yet, substantial off-label use
EP
occurs. It has been suggested that a serial microdroplet puncture technique for administration of highly purified liquid injectable silicone can significantly minimize the risk associated with cosmetic procedures involving the material.7,8 More concerning, as in our patient’s case, is the
AC C
illicit provision of nonmedical grade liquid injectable silicone by unlicensed practitioners.9 The complications caused by employing nonmedical grade liquid injectable silicone as a dermal filler are well established and reviewed in depth elsewhere.10 In the workup for fever of unknown origin, clues gleaned from history, physical
examination, and basic laboratory evaluations can often be misleading.11 However, in this patient’s situation, the history of silicone injections at the site of these plaques was not only tantamount to making the diagnosis but also the missing element that perpetuated an unnecessary workup. Diagnostic inquiries in patients with fever of unknown origin are frequently directed
ACCEPTED MANUSCRIPT 14-1813BordelonCHS, Page 5 of 7 toward uncovering a rheumatologic illness, an infectious disease, or a malignancy.12 In the pursuit of each of these entities as a potential cause of this patient’s fever, the final diagnosis was delayed. Therefore, clinicians should be careful to include etiologies like
adjuvants in the differential for fever of unknown origin.
MANAGEMENT
RI PT
inflammatory/granulomatous reactions and autoimmune/inflammatory syndrome induced by
Upon diagnosis, the patient began treatment with methylprednisolone, and her fever and malaise
SC
resolved. She was eventually transitioned from systemic corticosteroids to minocycline.
Although her fever and malaise had not recurred at her 8-month follow-up visit, she did report
M AN U
discomfort localized to the indurated plaques.
Management of autoimmune/inflammatory syndrome induced by adjuvants is adjuvantspecific and should be tailored to each patient’s particular manifestations.1 Although data are limited on treating silicone-induced systemic autoimmune/inflammatory responses, reports have shown that complete surgical excision can ameliorate symptoms.13,14 Other treatment options that have met with variable success include systemic steroids, minocycline, etanercept, allopurinol,
TE D
and pentoxifylline.15-19
It is important to note that silicone-induced systemic and granulomatous reactions can develop years after the injection. As such, patients may not immediately divulge a history of silicone augmentation to their providers; they may not realize that a past exposure is relevant.
EP
For that reason, direct questioning about exposure to adjuvants, such as liquid injectable silicone, should be part of the workup for a patient with fever of unknown origin. This careful practice can
AC C
give insightful clues into the source of fever before extensive workups are conducted and empirical treatment is administered. Lastly, practitioners should advise patients interested in liquid injectable silicone filler to avoid unlicensed practitioners and nonmedical grade products.
References
1. Perricone C, Colafrancesco S, Mazor RD, Soriano A, Agmon-Levin N, Shoenfeld Y. Autoimmune/inflammatory syndrome induced by adjuvants (ASIA) 2013: unveiling the pathogenic, clinical, and diagnostic aspects. J Autoimmun. 2013;47:1-16.
ACCEPTED MANUSCRIPT 14-1813BordelonCHS, Page 6 of 7 2. Altmeyer MD, Anderson LL, Wang AR. Silicone migration and granuloma formation. J Cosmet Dermatol. 2009;8:92-97.
3. Schmid A, Tzur A, Leshko L, Krieger BP. Silicone embolism syndrome: a case report, review of the literature, and comparison with fat embolism syndrome. Chest. 2005;127:2276-2281.
RI PT
4. Price EA, Schueler H, Perper JA. Massive systemic silicone embolism: a case report and review of literature. Am J Forensic Med Pathol. 2006;27:97-102.
5. Ellenbogen R, Rubin L. Injectable fluid silicone therapy. Human morbidity and mortality. JAMA. 1975;234:308-309.
SC
6. Restrepo CS, Artunduaga M, Carrillo JA, et al. Silicone pulmonary embolism: Report of 10 cases and review of the literature. Silicone pulmonary embolism: report of 10 cases and review of the literature. J Comput Assist Tomogr. 2009;33:233-237.
2):1530-1541.
M AN U
7. Duffy DM. Liquid silicone for soft tissue augmentation. Dermatol Surg. 2005;31(11 Pt 8. Orentreich DS. Liquid injectable silicone: Techniques for soft tissue augmentation. Clin Plast Surg. 2000;27:595-612.
9. Ellis LZ, Cohen JL, High W. Granulomatous reaction to silicone injection. J Clin Aesthet Dermatol. 2012;5:44-47.
TE D
10. Styperek A, Bayers S, Beer M, Beer K. Nonmedical-grade injections of permanent fillers: medical and medicolegal considerations. J Clin Aesthet Dermatol. 2013;6:22-29.
11. Bleeker-Rovers CP, Vos FJ, de Kleijn EM, et al. A prospective multicenter study on fever of unknown origin: the yield of a structured diagnostic protocol. Medicine (Baltimore).
EP
2007;86:26-38.
12. Zenone T. Fever of unknown origin in adults: Evaluation of 144 cases in a non-university hospital. Scand J Infect Dis. 2006;38:632-638.
AC C
13. Copeland M, Kressel A, Spiera H, Hermann G, Bleiweiss IJ. Systemic inflammatory disorder related to fibrous breast capsules after silicone implant removal. Plast Reconstr
Surg. 1993;92:1179-1181.
14. Kappel RM, Pruijn GJ. The monobloc hydrogel breast implant, experiences and ideas. Eur J Plast Surg. 2012;35:229-233.
15. Genovese MC. Fever, rash, and arthritis in a woman with silicone gel breast implants. West J Med. 1997;167:149-158.
ACCEPTED MANUSCRIPT 14-1813BordelonCHS, Page 7 of 7 16. Arin MJ, Bäte J, Krieg T, Hunzelmann N. Silicone granuloma of the face treated with minocycline. J Am Acad Dermatol. 2005;52(2 Suppl 1):53-56.
17. Desai AM, Browning J, Rosen T. Etanercept therapy for silicone granuloma. J Drugs Dermatol. 2006;5:894-896.
RI PT
18. Redondo P, Del Olmo J, Alberola I. In situ and distant foreign body granulomas caused by silicone. Treatment with allopurinol. Br J Dermatol. 2005;152:1064-1065.
19. Teuber SS, Reilly DA, Howell L, Oide C, Gershwin ME. Severe migratory granulomatous
SC
reactions to silicone gel in 3 patients. J Rheumatol. 1999;26:699-704.
Figure 1. The patient had a hyperpigmented, indurated, warm, exquisitely tender plaque on the
M AN U
external right buttock and the posteriolateral thigh.
Figure 2. T1-weighted magnetic resonance imaging of the pelvis with contrast enhancement and fat suppression demonstrated a heterogeneous appearance within the soft tissues surrounding the buttocks. This was representative of an intense inflammatory process. Numerous areas of signal void were consistent with silicone deposits.
TE D
Figure 3. A biopsy sample of the indurated plaque was stained with hematoxylin and eosin. A, A granulomatous inflammatory infiltrate was seen in the reticular dermis, bar = 200 µm. B, Clear, nonbirefringent vacuoles were visualized at the inferior portion of the specimen consistent with
EP
silicone, bar = 200 µm. C, Magnification highlighted vacuoles with a Swiss-cheese-like
AC C
appearance, 50 µm.
AC C
EP
TE D
M AN U
SC
RI PT
ACCEPTED MANUSCRIPT
AC C
EP
TE D
M AN U
SC
RI PT
ACCEPTED MANUSCRIPT
AC C
EP
TE D
M AN U
SC
RI PT
ACCEPTED MANUSCRIPT
