Advertisement

Characteristics and treatment of silicone granulomas: A retrospective multicenter cohort of 21 patients

Open AccessPublished:April 27, 2021DOI:https://doi.org/10.1016/j.jdin.2021.03.007
      To the Editor: In 2017, the United States Food and Drug Administration issued a warning against injectable silicone for body contouring after reports of serious complications.
      FDA Warns Against Use of Injectable Silicone for Body Contouring and Enhancement: FDA Safety Communication.
      Despite this, and given its low cost and relative permanence, injectable silicone remains offered in some countries and occasionally off-label within the United States.
      • Wang L.L.
      • Thomas W.W.
      • Friedman O.
      Granuloma formation secondary to silicone injection for soft-tissue augmentation in facial cosmetics: mechanisms and literature review.
      Silicone granulomas (SGs) are the granulomatous responses that may occur after silicone injection or implant rupture.
      • Wang L.L.
      • Thomas W.W.
      • Friedman O.
      Granuloma formation secondary to silicone injection for soft-tissue augmentation in facial cosmetics: mechanisms and literature review.
      • Price E.A.
      • Schueler H.
      • Perper J.A.
      Massive systemic silicone embolism: a case report and review of literature.
      • Austad E.D.
      Breast implant-related silicone granulomas: the literature and the litigation.
      Limited data on patients with SG are available. The largest cohort to date consists of only 9 patients.
      • Price E.A.
      • Schueler H.
      • Perper J.A.
      Massive systemic silicone embolism: a case report and review of literature.
      We sought to characterize patients with SG in a retrospective multicenter cohort.
      The Research Patient Data Registry, associated with Mass General Brigham hospitals, was queried using SG-related International Classification of Diseases 9/10 codes and terms. Demographics, clinical features, and treatment data were collected and analyzed, with P values of ≤.05 considered statistically significant.
      We identified 21 patients with SG, 14 from silicone injections most commonly into the buttocks (57%, 8/14) and 7 from ruptured silicone breast implants (Table I). Compared with the implant group, the injection group included a significant number of Latino patients (64%, 9/14, < .01), patients having procedures outside the United States. (57%, 8/14, P = .02), and patients misinformed about the materials used or body parts injected (57%, 8/14, P = .02). Additionally, only the injection group included Medicaid (29%, 4/14), uninsured (7%, 1/14), and transgender patients (14%, 2/14).
      Table IDemographics and clinical features of patients with silicone granulomas
      DemographicsSilicone injection group (n = 14) n (%)Silicone implant group (n = 7) n (%)P value
      P values based on Fisher's exact test unless otherwise specified; all P values calculated using STATA version 15.1 (StataCorp).
      Age at diagnosis, median (range), years43.3 (24.5-71.9)67.8 (44.6-79.1).03
      P values based on Mann-Whitney test.
      Gender identity.36
       Cisgender women10 (71)7 (100)
       Cisgender men2 (14)0
       Transgender women2 (14)0
      Race/ethnicity
       Latinx9 (64)0<.01
       White4 (29)6 (86).02
       Middle Eastern1 (7)01
       Asian01 (14).33
      Insurance type.42
       Medicare6 (43)5 (71)
       Medicaid4 (29)0
       Private3 (21)2 (29)
       Uninsured1 (7)0
      Procedure performed outside the United States
      Procedure performed in Dominican Republic (n = 4), Republic of Colombia (n = 1), Mexico (n = 1), United Arab Emirates (n = 1), and an unspecified country in South America (n = 1).
      8 (57)0.02
      Misinformed about procedure8 (57)0.02
      Reason for silicone administration.19
       Augmentation11 (79)5 (71)
       Gender confirmation2 (14)0
       Reconstruction02 (29)
       Unspecified1 (7)0
      Site of silicone administration
       Buttocks8 (57)0<.01
       Breasts5 (36)7 (100).06
       Lower extremities3 (21)0.52
       Face2 (14)0.53
       Upper extremities1 (7)01
      Signs and symptoms
       Pain9 (64)3 (43).40
       Erythema6 (42)0.06
       Edema6 (42)0.06
       Induration5 (36)1 (14).61
       Pruritus3 (21)0.52
       Hyperpigmentation3 (21)0.52
       Warmth1 (7)1 (14)1
      Number of signs and symptoms.03
       0-12 (14)5 (71)
       2-37 (50)2 (29)
       ≥45 (36)0
      Migration of silicone.48
       Local
      From breasts to axillary lymph nodes (n = 4), legs to ankles (n = 2), and buttocks to anterior pelvis (n = 1).
      4 (29)3 (43)
       Distant
      From breasts to nose (n = 1), breasts to abdominal soft tissues (n = 1), and breasts and buttocks to lungs and abdominal soft tissues (n = 1).
      3 (21)0
      Time between silicone administration and symptom onset, median (range), years5.0 (1.0-48.0)

      (n = 11)
      30.0 (21.0-46.0)

      (n = 4)
      .05
      P values based on Mann-Whitney test.
      Time between symptom onset and diagnosis, median (range), months5.8 (0.5-122.3)

      (n = 11)
      4.1 (1.5-9.8)

      (n = 5)
      .77
      P values based on Mann-Whitney test.
      Method of diagnosis1
       Biopsy only2 (14)1 (14)
       Imaging only
      Magnetic resonance imaging (n = 10), computed tomography (n = 9), and ultrasound (n = 9).
      2 (14)1 (14)
       Both biopsy and imaging
      Magnetic resonance imaging (n = 10), computed tomography (n = 9), and ultrasound (n = 9).
      10 (71)5 (71)
      Tissue cultures performed to exclude concurrent infection7 (50)1 (14).17
      Developed autoimmune disease after silicone exposure
      Celiac disease (n = 1).
      1 (6)01
      Follow-up period, median (range), months28.3 (2.1-180.4)8.5 (0.07-145.7).12
      P values based on Mann-Whitney test.
      Bolded numbers indicate statistical significance.
      P values based on Fisher's exact test unless otherwise specified; all P values calculated using STATA version 15.1 (StataCorp).
      P values based on Mann-Whitney test.
      Procedure performed in Dominican Republic (n = 4), Republic of Colombia (n = 1), Mexico (n = 1), United Arab Emirates (n = 1), and an unspecified country in South America (n = 1).
      § From breasts to axillary lymph nodes (n = 4), legs to ankles (n = 2), and buttocks to anterior pelvis (n = 1).
      From breasts to nose (n = 1), breasts to abdominal soft tissues (n = 1), and breasts and buttocks to lungs and abdominal soft tissues (n = 1).
      Magnetic resonance imaging (n = 10), computed tomography (n = 9), and ultrasound (n = 9).
      # Celiac disease (n = 1).
      Compared with implant patients, injected patients had more signs and symptoms (P = .03), with symptoms developing a median of 25 years sooner after silicone administration (P = .05, Table I). Only injected patients had silicone migration to distant sites (21%, 3/14), including 1 patient who presented with a life-threatening migration to the lungs.
      Thirty-six percent (5/14) of injected patients were treated medically, 43% (6/14) surgically, and 7% (1/14) both medically and surgically. The most common medical therapies were systemic steroids (29%, 4/14), hydroxychloroquine (29%, 4/14), tetracyclines (29%, 4/14), and adalimumab (14%, 2/14) (Table II). Thirty-three percent (2/6) of medically treated injected patients had complete response (CR); 1 patient received hydroxychloroquine and adalimumab followed by adalimumab monotherapy, whereas the other received hydroxychloroquine, minocycline, and prednisone followed by hydroxychloroquine monotherapy. Both patients continued their final monotherapy without taper and were able to maintain CR. Although no surgically treated injected patients had CR, most (86%, 6/7) implant patients had CR to surgery.
      Table IITreatment modalities and outcomes of patients with silicone granulomas
      Treatment modalitiesSilicone injection group (n = 14) n (%)
      All percentages based on denominator as defined by n in the first row unless otherwise specified by n in the first column.
      Silicone implant group (n = 7) n (%)
      All percentages based on denominator as defined by n in the first row unless otherwise specified by n in the first column.
      P value
      P values based on Fisher's exact test unless otherwise specified; all P values calculated using STATA version 15.1 (StataCorp).
      Treatment
       Medical5 (36)0.12
       Surgical6 (43)7 (100).02
       Medical and surgical1 (7)01
       No treatment because of comorbidities2 (14)0.53
      Medical treatments
      Medical treatment duration was at least 2 months.
       Intralesional steroids1 (7)N/A-
       Systemic steroids4 (29)N/A-
       Hydroxychloroquine4 (29)N/A-
       Tetracycline antibiotics4 (29)N/A-
       Methotrexate1 (7)N/A-
       Mycophenolate mofetil1 (7)N/A-
       Adalimumab2 (14)N/A-
      Medical treatment (n = 6 for injection group)
       Complete response
      Complete and partial responses were defined as complete and partial improvement, respectively, of physician-observed signs and patient-reported symptoms in Table I.
      2 (33)N/A-
       Partial response4 (67)N/A-
      Number of medical treatments per patient, median (range)
       Complete response2.5 (2-3)N/A-
       Partial response3 (1-5)N/A-
      Surgical treatment (n = 7 for each group)<.01
       Complete response06 (86)
       Partial response7 (100)1 (14)
      Long-term contour change/scarring.17
       Medical treatment (n = 6 for injection group)2 (33)N/A
       Surgical treatment (n = 7 for each group)3 (43)1 (14)
       No treatment (n = 2 for injection group)2 (100)N/A
      Bolded numbers indicate statistical significance.
      N/A, Not applicable.
      P values based on Fisher's exact test unless otherwise specified; all P values calculated using STATA version 15.1 (StataCorp).
      All percentages based on denominator as defined by n in the first row unless otherwise specified by n in the first column.
      Medical treatment duration was at least 2 months.
      § Complete and partial responses were defined as complete and partial improvement, respectively, of physician-observed signs and patient-reported symptoms in Table I.
      SGs from injectable silicone disproportionately affected racial/ethnic, socioeconomic, and gender minorities and were associated with greater morbidity. Concordant with existing limited literature, medical therapy was more effective compared with surgery for SGs from injectable silicone,
      • Wang L.L.
      • Thomas W.W.
      • Friedman O.
      Granuloma formation secondary to silicone injection for soft-tissue augmentation in facial cosmetics: mechanisms and literature review.
      ,
      • Price E.A.
      • Schueler H.
      • Perper J.A.
      Massive systemic silicone embolism: a case report and review of literature.
      whereas surgery was the treatment of choice for SGs from ruptured implants.
      • Austad E.D.
      Breast implant-related silicone granulomas: the literature and the litigation.
      This difference is explained by the greater propensity of injected silicone to migrate, making it challenging to fully remove surgically, as compared with the silicone gel in implants.
      • Wang L.L.
      • Thomas W.W.
      • Friedman O.
      Granuloma formation secondary to silicone injection for soft-tissue augmentation in facial cosmetics: mechanisms and literature review.
      ,
      • Price E.A.
      • Schueler H.
      • Perper J.A.
      Massive systemic silicone embolism: a case report and review of literature.
      Akin to the treatment algorithm for cutaneous sarcoidosis,
      • Caplan A.
      • Rosenbach M.
      • Imadojemu S.
      Cutaneous sarcoidosis.
      our results suggest that systemic steroids, hydroxychloroquine, and tetracyclines should be considered as first-line agents for SGs from injectable silicone, followed by tumor necrosis factor-alpha inhibitors for refractory disease. Study limitations include the small sample size and retrospective methodology. Further investigation, particularly regarding SG treatment, is warranted.

      Conflicts of interest

      None disclose.

      References

      1. FDA Warns Against Use of Injectable Silicone for Body Contouring and Enhancement: FDA Safety Communication.
        • Wang L.L.
        • Thomas W.W.
        • Friedman O.
        Granuloma formation secondary to silicone injection for soft-tissue augmentation in facial cosmetics: mechanisms and literature review.
        Ear Nose Throat J. 2018; 97: E46-E51
        • Price E.A.
        • Schueler H.
        • Perper J.A.
        Massive systemic silicone embolism: a case report and review of literature.
        Am J Forensic Med Pathol. 2006; 27: 97-102
        • Austad E.D.
        Breast implant-related silicone granulomas: the literature and the litigation.
        Plast Reconstr Surg. 2002; 109 (discussion 1731-1732): 1724-1730
        • Caplan A.
        • Rosenbach M.
        • Imadojemu S.
        Cutaneous sarcoidosis.
        Semin Respir Crit Care Med. 2020; 41: 689-699