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Progressive granulomatous pneumonitis in response to cosmetic subcutaneous silicone injections in a patient with HIV-1 infection: case report and review of the literature.

The injection of silicone is commonly used in cosmetic and reconstructive procedures owing to its ability to enhance tissue volume, most commonly of the breasts or buttocks, and because of its durability, weak antigenicity, and noncarcinogenicity. (1) However, silicone injections can also produce complications, including local infection, tissue necrosis, foreign body giant cell reactions, regional lymphadenopathy, and acute systemic illness. (1,2) Many case reports attribute "siliconomas" to silicone implants that subsequently rupture. (2,3) Subcutaneous silicone injections have led to acute pulmonary dysfunction due to silicone pulmonary emboli, acute pneumonitis, acute pulmonary hemorrhage, diffuse alveolar damage, acute granulomatous pneumonitis, and lymphadenitis, with subsequent deaths. (1,2,4-10) In most of these cases, patients developed acute respiratory disease within days of the procedure. However, there have been no reported descriptions of chronic pulmonary disease and the associated pathologic changes in response to silicone to date. Additionally, there are only rare reports of silicone-induced pulmonary disease in human immunodeficiency virus 1 (HIV-1)-infected individuals. (9-11) We present a case of chronic, progressive granulomatous pneumonitis in response to subcutaneous silicone injections in an HIV-1-infected, transgender male-to-female patient who developed acute pneumonitis followed by pulmonary disease progression 4 years later, associated with irregular compliance with highly active antiretroviral therapy (HAART).


A 39-year-old transgendered female (genetic XY male) from Central America presented with acute dyspnea, bilateral pleuritic chest pain, subjective fever, chills, and nonproductive cough. She had been diagnosed with HIV-1 infection 22 months before presentation and treated with HAART consisting of lamivudine, zidovudine, and efavirenz. Undetectable HIV-1 viral loads were achieved during the first 6 months of therapy, but the patient subsequently reported intermittent adherence to HAART, associated with a slowly increasing plasma HIV-1 RNA viral load (to 1000-3600 copies/mL). Peripheral blood [CD4.sup.+] lymphocyte levels were stable (160-170 cells/[micro]L). One week before presentation (18 months after virologic failure), she traveled to Mexico for silicone injections in the breasts and buttocks.

Chest computed tomography (CT) revealed diffuse, bilateral peripheral interstitial air-space opacities, raising concern for opportunistic infection. Multiple nodular soft tissue densities were seen overlying the breasts and buttocks, attributable to silicone injections. She was treated empirically with vancomycin, ampicillin, ceftazidime, trimethoprim/sulfamethoxazole, and prednisone and received ganciclovir owing to concern for cytomegalovirus infection. Sputum samples were negative for microorganisms, as were serum assays for cytomegalovirus and cryptococcal antigens. Within days, she reported symptomatic improvement; she was discharged and prescribed HAART, trimethoprim/sulfamethoxazole as prophylaxis, and a short course of prednisone. At the time of presentation, the HIV-1 RNA load was 80 000 copies/mL, and CD4 counts were greater than 200/uL. Five months after discharge, the HAART regimen was changed on the basis of genotype-resistance testing. She responded well to the new regimen, with suppression of HIV RNA to below assay limit of detection, with CD4 cell counts of 220-240/[micro]L.



One year after discharge, she was seen in the emergency department for worsening shortness of breath, cough, and fatigue. Chest radiography and CT scan showed persistent radiographic changes, and HIV RNA levels remained suppressed.

She was symptomatically stable until 2 years later, when she presented with worsening dyspnea and cough productive of yellow sputum. Chest CT showed diffuse ground-glass opacities, septal thickening, and numerous irregular nodules that had increased in size and become more confluent (Figure 1, A). She was treated presumptively for Pneumocystis jiroveci pneumonia and community-acquired pneumonia, until an extensive evaluation again excluded infectious etiologies. She reported intermittent adherence to the HAART regimen and had detectable HIV viremia (1590 copies/mL) with CD4 cell counts of 185/[micro]L.

Pulmonary function tests showed decreased single-breath diffusion capacity. Eighteen months after discharge and 4 years after initial presentation, the patient experienced a marked increase in dyspnea and cough. Chest CT revealed progression of diffuse ground-glass opacities both in size and confluence (Figure 1, B). She underwent video-assisted thoracoscopic surgical biopsies of the right lung. Bronchial washings from the right lung were negative for microbial infection.


Light Microscopy

The right upper lobe and right lower lobe lung wedge biopsy specimens were fixed in neutral buffered formalin, embedded into paraffin, and sectioned into 5-mm-thick sections. Morphologic characteristics were assessed on standard hematoxylin-eosin-stained sections.


Microscopic examination showed innumerable spheroid structures, ranging from 10 to 160 [micro]m, with a thin eosinophilic capsule and cleared core, diffusely throughout the lung parenchyma (Figure 2, A) and within intravascular spaces (Figure 2, B). Spheroids were surrounded by foreign body giant cells with adjacent nonnecrotizing granulomatous inflammation showing compact epithelioid histiocytes, lymphocytes, plasma cells, and mild fibrosis. There were small foci of intra-alveolar fibrin deposition, indicating active injury. Oil Red O staining for lipid was negative. Histochemical staining results were negative for organisms. Immunohistochemical staining for CD68 highlighted numerous macrophages, with a dominance of CD4 lymphocytes in proximity to the microgranulomas. CD31 staining of vascular endothelium confirmed the presence of intravascular silicone particles. The findings were judged to reflect a granulomatous reaction to silicone.

Electron Microscopy

Fresh tissue was prepared for electron microscopy by placing a portion of each wedge biopsy specimen into a glutaraldehyde fixative (2.5% glutaraldehyde, 2% paraformaldehyde, and 0.025% calcium chloride in a 0.1M sodium cacodylate buffer, pH 7.4) with subsequent processing in an Electron Microscopy Sciences (Hatfield, Pennsylvania) Lynx Vision automatic tissue processor. The tissue was postfixed in osmium tetroxide, stained en bloc with uranyl acetate, dehydrated in graded ethanol solutions, infiltrated with propylene oxide/Epon mixtures, embedded in pure Epon, and polymerized overnight at 60 [degrees]C. One-micron sections were cut, stained with toluidine blue, and examined by light microscopy. Representative areas were chosen for electron microscopic evaluation. Thin sections were cut with an ultramicrotome and diamond knife and stained with lead citrate. Examination of sections with an FEI Morgagni transmission electron microscope (Hillsboro, Oregon) revealed numerous silicone particles within the lung parenchyma, alveolar space, and within small pulmonary vessels. Images were captured with an Advanced Microscopy Techniques (Woburn, Massachusetts) digital charge-coupled device camera (Figure 3).


Subcutaneous silicone injections can yield significant complications, including local infection and necrosis, as well as silicone pulmonary emboli, acute pulmonary hemorrhage, acute pneumonitis, and diffuse alveolar damage. Silicone pulmonary embolism is proposed to result from increased tissue pressures at injection sites, local massage of the site, or the inadvertent direct intravenous injection of silicone particles. (4-10) To date, there have been no case reports describing chronic pulmonary pathology resulting from silicone injection and there is little literature on silicone-induced pulmonary disease in HIV-1-infected individuals. (9-11) In the present case, an active persistent granulomatous pneumonitis developed in response to subcutaneous silicone injections during a 4-year period in an HIV-1-infected, transgender patient receiving HAART irregularly.

There are few reported cases of silicone-induced pneumonitis in HIV-1-infected patients (Table). (9-11) Two case reports (9,10) describe acute respiratory failure within 1 day of receiving subcutaneous silicone injections. In 1 case, a transbronchial biopsy was obtained, showing intra-alveolar hemorrhage with fibrin, inflamed alveolar walls, and silicone particles within interstitial capillaries. (9) In the second case, postmortem examination 3 weeks subsequent to receiving silicone injections revealed diffuse alveolar damage and a foreign body reaction to silicone microemboli. (10)

Males et al (11) reported 3 cases of granulomatous disease in HIV-1-infected patients 2 to 3 years after receiving subcutaneous silicone injections: 1 with injection site (hip) granulomatous disease and 2 with additional pulmonary and/or hepatic granulomatous disease diagnosed primarily by clinical information and increased uptake on gallium Ga 67 scans. None of these patients experienced pulmonary symptoms. A transbronchial biopsy specimen was obtained from 1 patient with chest CT findings, in addition to gastric and ileocolic biopsy specimens. All biopsy specimens displayed the presence of epithelioid granulomas without central necrosis. However, no silicone particles were identified in any of the biopsy samples, thus the diagnosis of silicone-induced pneumonitis could not be confirmed.

Silicone is recognized to be weakly antigenic. In view of the patient's irregular HAART therapy and shifting [CD4.sup.+] lymphocyte counts, we speculate that immune reconstitution may have played a role in the progression of this patient's disease. The prognosis of patients infected with HIV-1 has significantly improved since the institution of HAART as standard care, enabling substantial improvements in immunologic and virologic parameters, with a steep decline in morbidity and mortality rates. However, a subset of patients will develop an immune reconstitution inflammatory syndrome (IRIS) days to months following the initiation of HAART, as an adverse effect of immune reconstitution and increased cell-mediated immunity. This syndrome has been reported in response to a variety of infective microorganisms, including Mycobacterium avium-intracellulare, Mycobacterium tuberculosis, cytomegalovirus, herpes simplex virus, parvovirus, varicella-zoster virus, hepatitis B and C viruses, and cryptococcus. (12,13) There have also been rare reports of IRIS occurring in response to "inert" tattoo pigments. (14) Murray et al (15) reported the case of a 66-year-old HIV-positive man who, several months after initiating HAART, experienced an exacerbation of multiple foreign body granulomas at the site of preexisting traumatic scars decades after the original injuries; however, no specific endogenous or exogenous antigen was identified.

Although impossible to prove on the basis of a single case and absence of clear criteria for establishing IRIS as the cause of disease in the present setting, the presence of both foreign body and immune microgranulomas, waxing and waning symptomatology, and radiographic progression with reduction in diffusion capacity are all consistent with an active cell-mediated response to silicone. Although intercurrent infections are always a concern in the immunosuppressed host, extensive diagnostic tests and histologic examination effectively exclude a role for occult infection. Additional studies will be required to evaluate the possible role of IRIS in HIV-1-infected patients with chronic silicone-induced pneumonitis.


(1.) Narins RS, Beer K. Liquid injectable silicone: a review of its history, immunology, technical considerations, complications, and potential. Plast Reconstr Surg. 2006; 118(3 suppl):77S-84S.

(2.) Christensen L. Normal and pathologic tissue reactions to soft tissue gel fillers. Dermatol Surg. 2007; 33(suppl 2):S168-S175.

(3.) Dragu A, Theegarten D, Bach AD, et al. Intrapulmonary and cutaneous siliconomas after silent silicone breast implant failure. Breast J. 2009; 15(5):496499.

(4.) Chastre J, Basset F, Viau F, et al. Acute pneumonitis after subcutaneous injections of silicone in transsexual men. N Engl J Med. 1983; 308(13):764-767.

(5.) Chastre J, Brun P, Soler P, et al. Acute and latent pneumonitis after subcutaneous injections of silicone in transsexual men. Am Rev Respir Dis. 1987; 135(1):236-240.

(6.) Gurvits GE. Silicone pneumonitis after a cosmetic augmentation procedure. N Engl J Med. 2006; 354(2):211-212.

(7.) Parikh R, Karim K, Parikh N, et al. Case report and literature review: acute pneumonitis and alveolar hemorrhage after subcutaneous injection of liquid silicone. Ann Clin Lab Sci. 2008; 38(4):380-385.

(8.) Price EA, Schueler H, Perper JA. Massive systemic silicone embolism: a case report and review of literature. Am J Forensic Med Pathol. 2006; 27(2):97-102.

(9.) Schmid A, Tzur A, Leshko L, et al. Silicone embolism syndrome: a case report, review of the literature, and comparison with fat embolism syndrome. Chest. 2005; 127(6):2276-2281.

(10.) Clark RF, Cantrell FL, Pacal A, et al. Subcutaneous silicone injection leading to multi-system organ failure. Clin Toxicol (Phila). 2008; 46(9):834-837.

(11.) Males S, Joly V, Adle-Biassette H, et al. Silicone in HIV-1-infected patients: a cause of misdiagnosed granulomatous disease. Int J Infect Dis. 2010; 14(suppl 3): e277-e279.

(12.) Muller M, Wandel S, Colebunders R, et al. Immune reconstitution inflammatory syndrome in patients starting antiretroviral therapy for HIV infection: a systematic review and meta-analysis. Lancet Infect Dis. 2010; 10(4): 251-261.

(13.) Hirsch HH, Kaufmann G, Sendi P, et al. Immune reconstitution in HIV infected patients. Clin Infect Dis. 2004; 38(8):1159-1166.

(14.) Silvestre JF, Albares MP, Ramon R, et al. Cutaneous intolerance to tattoos in a patient with human immunodeficiency virus: a manifestation of the immune restoration syndrome. Arch Dermatol. 2001; 137(5):669-670.

(15.) Murray CA, DeKoven J, Spaner DE. Foreign body granuloma: a new manifestation of immune restoration syndrome. J Cutan Med Surg. 2003; 7(1): 38-42.

Lida P. Hariri, MD, PhD; Henning A. Gaissert, MD; Robert Brown, MD; Andrea Ciaranello, MD, MPH; Reginald E. Greene, MD; Martin K. Selig, BA; Richard L. Kradin, MD

Accepted for publication May 3, 2011.

From the Departments of Pathology (Drs Hariri and Kradin and Mr Selig), Medicine (Drs Brown, Ciaranello, and Kradin), Surgery (Dr Gaissert), and Radiology (Dr Greene), Massachusetts General Hospital, Boston.

The authors have no relevant financial interest in the products or companies described in this article.

Reprints: Lida Hariri, MD, PhD, Department of Pathology, Massachusetts General Hospital, 55 Fruit St, Warren Bldg, Room 219, Boston, MA 02114 (e-mail:
Reported Cases of Silicone Injection Leading to Silicone Pneumonitis
in HIV-1-Infected Patients

 Injection Symptom
Source, y Sex Site Onset Symptoms

Schmid 22/M Breasts 1d Cough, progressive
et al, (9) dyspnea, fever, chills

Clark et al, (10) 45/M Buttocks, 4h Cough, fever, lethargy
2008 thigh

Males 38/M Hips, 1y Fever, cervical
et al, (11) buttocks adenopathy,
2010 hepatosplenomegaly

 HIV Pathologic
Source, y Status Tissue Findings Outcome

Schmid + TBB Alveolar Discharge
et al, (9) hemorrhage 1 wk ap
2005 Alveolar

Clark et al, (10) + Autopsy Organizing Death
2008 pneumonia, 22 d ap
 DAD, and
 FBGCR with

Males + TBB Epithelioid Symptoms
et al, (11) granulomas resolved
2010 without
 No silicone

Abbreviations: ap, after silicone procedure; DAD, diffuse alveolar
damage; FBGCR, foreign body giant cell reaction; HIV-1, human
immunodeficiency virus 1; TBB, transbronchial biopsy; +, positive.
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Title Annotation:Case Report
Author:Hariri, Lida P.; Gaissert, Henning A.; Brown, Robert; Ciaranello, Andrea; Greene, Reginald E.; Selig
Publication:Archives of Pathology & Laboratory Medicine
Date:Feb 1, 2012
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