TOPICS

Indurated Plaques and Nodules on the Buttocks of a Young Healthy Female

Jason Emer, MD; Daniel Roberts, BS; Lauren Levy, BA; Harleen Sidhu, MD; Neil Fernandez, MD

Dr. Emer, Dr. Fernandez, and Ms. Levy are from Mount Sinai School of Medicine, Department of Dermatology, New York, New York. Mr. Roberts is from Stanford School of Medicine, Department of Pathology, Stanford, California. Dr. Sidhu is from Mount Sinai School of Medicine, Department of Pathology, New York, New York.

Case Report
A 30-year-old Dominican woman with no prior medical history presented to the outpatient dermatology clinic with complaints of severe pain, swelling, and “hardness” of both buttocks, which had steadily worsened over the past year. She reported no prior history of any skin problems. She denied any recent travel or trauma to the area, but reluctantly admitted to prior injections of an unknown substance into the buttock for cosmetic enhancement. The patient described an initial cosmetic improvement without complications, but steadily developed an increasing number of painful “bumps” that made it difficult to function normally, impeding her ability to comfortably sit or stand. Systemic symptoms, such as fever, joint pain, and chills were intermittently felt. Physical examination revealed edematous and diffuse woody indurated plaques and nodules of the bilateral buttocks that were tender to palpation (Figure 1). Inguinal lymphadenopathy was present, but no joint swelling was appreciated. A punch biopsy of the skin was sent for microscopic analysis (Figures 2 and 3).

Diagnosis
Silicone granuloma

Microscopic Findings and Clinical Course
Histopathology revealed disruption of the adipose tissue architecture with collections of a vacuolated material between collagen bundles in the deep dermis, admixed with histiocytes and rare giant cells (Figure 2). The nonstaining, nonpolarizable material was contained within histiocyes, and larger vacuoles present in the granuloma suggest the possibility of an adulterated mixture of nonmedical-grade silicone (Figure 3). This histopathological picture in the context of prior cosmetic injections at the same site was highly suggestive of a reaction to foreign material, so treatment was initiated without awaiting cultures or special stains.

The patient was treated with oral minocycline 100mg twice daily for three months with considerable reduction of erythema, woody induration, and the size of her buttocks, along with a notable decrease in pain and swelling (Figure 4). The patient reported improvement in systemic symptoms within two weeks of therapy and was able to resume her normal function without pain upon sitting or standing. The patient is currently on prolonged therapy without any complications.

Discussion
Silicone granulomas are an unfortunate complication of intradermal or subcutaneous silicone injection that presents as diffuse swelling, erythema, or indurated plaques and/or nodules that develop anywhere from months to years after initial filler placement.[1] Granulomas can arise both at the site of injection or distantly due to migration of the filler material.[2] These lesions have been reported in various locations, including the face, lips, eyelids, buttocks, and legs. Systemic symptoms, such as fever, weight loss, and nausea may occur in conjunction with classical skin findings.[3] Local spread of silicone or impure products, although rarely reported, can result in pneumonitis, hepatic granuloma formation, or even death, emphasizing the need for early recognition and treatment.[4,5]

Granulomatous responses from silicone injections can result from impure silicone or ingredient additives and/or poor injection technique. Placing too much product volume per session, not following a proper microdroplet injection technique, or procedures performed by nonlicensed injectors will increase the risk for complications.[6] Currently, the United States Food and Drug Administration has approved medical grade liquid silicone, Silikon 1000 (purified polydimethylsiloxane, Alcon Laboratoires Inc., Fort Worth, Texas) and Adatosil 5000 (Bausch & Lomb Inc., Rochester, New York), for cases of retinal detachment (optical use); cosmetic applications for these products are considered “off-label” uses. The listed products are composed of pure silicone and considered medical grade, while nonmedical-grade products are often adulterated with oil-based impurities.[7] These impurities may be identified microscopically as translucent bodies exhibiting birefringent properties, by analyzing dispersion patterns in electron microscopy, or by spectroscopy.[8]

Histologically, lesions represent a localized foreign body granulomatous response to either the silicone itself or to an added product.[9] Although the exact pathogenesis of granuloma formation in this setting has not been fully elucidated, it is believed to be a host immune response blockading a foreign substance too large for macrophage digestion.[10] Extensive clinical variability is observed in patients who develop granulomatous reactions following silicone injection, leading to the hypothesis that secondary triggers, such as an infectious process or trauma, may stimulate immunological cross-reactions and subsequent granuloma formation.[1,6,10] Lesions may also act as a nidus for infection due to restricted local blood flow from the surrounding fibrous reaction; thus, tissue cultures should be sent to rule out mycobacterial, fungal, and bacterial infections. In complicated cases suggestive of a secondary infection, specialized stains, such as acid-fast bacilli (AFB) and Grocott’s methenamine silver (GMS), or specific tests, such as polymerase chain reaction (PCR), may be warranted as well.[2,6] In a patient with a clear history of cosmetic treatment in the affected area with an initial biopsy indicating a foreign body reaction without evidence of infection, cultures or special stains are not necessary and swift initiation of empiric treatment is advised.

As granulomatous inflammation requires time to manifest, there is often a latency period between the initial placement of the product and the appearance of skin lesions or associated symptoms. Infectious, malignant, and autoimmune diseases should be considered in the differential diagnosis. Granulomatous processes secondary to infection include cutaneous tuberculosis, leprosy, and deep fungal infections. These can be differentiated with a combination of cultures, routine, and specialized staining, such as AFB and GMS. Antibodies to phenolic glycolipid-1 are specific for Mycobacterium leprae, although their clinical utility is questionable. PCR testing for mycobacterium species is also recommended if clinical suspicion for tuberculosis or leprosy is high and AFB staining fails to identify organisms. Systemic symptoms of pulmonary infection or peripheral neuropathies may also prove diagnostically useful.

Noninfectious granulomatous diseases must also be considered in the differential diagnosis. Sarcoidosis is a multisystemic disease, although it may present strictly with cutaneous manifestations. Clinically, red-brown papules and plaques that may mimic the appearance of foreign body reactions characterize sarcoidosis most commonly. Histological analysis can distinguish these entities and microscopic sections of sarcoidal lesions will reveal noncaseating granulomas ringed by Langhan’s giant cells, which may contain nonspecific asteroid or Schaumann bodies. Both calcium and angiotensin converting enzyme (ACE) levels can be elevated in sarcoidosis; thus, serology may aid in diagnosis. Granuloma annulare (GA), especially the subcutaneous type, can also mimic foreign body granulomas clinically, but microscopic examination will reveal palisading histiocytes surrounding a necrobiotic core. No foreign material will be evident and granulomas will often contain abundant mucin. Attaining a complete history will identify other clinically similar entities, such as a history of Crohn’s disease, rheumatoid arthritis, or prior exposure to beryllium, which may all present with cutaneous manifestations.

Although there is no standardized treatment for silicone granulomas, there have been numerous reports of therapeutic success with various treatment methods. Surgical excision may be curative if the granulomas are well-circumcised, but may leave unsightly scars. Both intralesional and oral steroids have been attempted with inconsistent results; some lesions resolved completely while others showed little improvement.[11] Oral steroids, in particular, may result in temporary resolution with a reappearance of the lesion during the tapering period and is generally not recommended. Conversely, intralesional triamcinolone acetonide (ILTAC 10–40mg/mL) injected on a weekly basis has been shown to improve lesions, although patients must be monitored for atrophy. Intralesional 5-fluorouracil (5-FU) can be combined with intralesional corticosteroid injections if corticosteroids alone fail to demonstrate improvement after 2 to 3 months of treatment.[12] The antimitotic properties of 5-FU have improved the erythema, induration, and the progression of facial granulomas arising as complications of dermal filler use.[11,13,14] Bleomycin, another antimitotic agent, has been shown to reduce hypertrophic scars and keloids; thus, both 5-FU and bleomycin should be considered for adjuvant treatment of granulomatous foreign body reactions that fail to resolve with ILTAC alone.[15]

Antibiotics, such as minocycline, have also been reported to improve granulomatous lesions at both high (100mg orally twice daily) and low doses (100mg orally once daily).[16] If minocycline is ineffective, different antibiotics, such as tetracyline (500mg orally twice daily), have been administered with success.[3] Resistant GA has been completely cleared with the monthly antibiotic regimen of oral rifampin (600mg), ofloxacin (400mg), and minocycline hydrochloride (100mg) in a timeframe ranging from 3 to 5 months.[17] This regimen is effective for the treatment of tubercouloid leprosy, which has a similar histological and clinical appearance to GA. The use of this combination in other granulomatous diseases, including foreign body reaction, may therefore show clinical utility.

Immunomodulating medications, such as topical imiquimod cream or subcutaneous injections of etanercept, may also have a role in treating more recalcitrant lesions. The use of imiquimod 5% cream applied twice a day for two months has improved lip granulomas.[18] Doses of either 25 or 50mg of etanercept subcutaneous twice weekly for 1 to 2 months has shown to either significantly reduce erythema and tenderness or fully resolve granulomas of the buttocks and upper thigh in three cases.[19,20] Further studies are needed to assess the efficacy of the various treatment modalities reported in the literature.

References
1.    Rapaport MJ, Vinnik C, Zarem H. Injectable silicone: cause of facial nodules, cellulitis, ulceration, and migration. Aesthetic Plast Surg. 1996;20:267–276.
2.    Altmeyer MD, Anderson LL, Wang AR. Silicone migration and granuloma formation. J Cosmet Dermatol. 2009;8:92–97.
3.    Lopiccolo MC, Workman BJ, Chaffins ML, Kerr HA. Silicone granulomas after soft-tissue augmentation of the buttocks: a case report and review of management. Dermatol Surg. 2011;37:720–725.
4.    Brown SL, Silverman BG, Berg WA. Rupture of silicone-gel breast implants: causes, sequelae, and diagnosis. Lancet. 1997;350(9090):1531–1537.
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11.    Lemperle G, Gauthier-Hazan N. Foreign body granulomas after all injectable dermal fillers: part 2. Treatment options. Plast Reconstr Surg. 2009;123:1864–1873.
12.    De Maio M, Rzany B. Injectable Fillers in Aesthetic Medicine. New York: Springer; 2006: 67–78.
13.    Fitzpatrick RE. Treatment of inflamed hypertrophic scars using intralesional 5-FU. Dermatol Surg. 1999;25:224–232.
14.    Lemperle G, Rullan PP, Gauthier-Hazan N. Avoiding and treating dermal filler complications. Plast Reconstr Surg. 2006;118(3 Suppl):92S–107S.
15.    Espana A, Solana T, Quintanilla E. Bleomycin in the treatment of keloids and hypertrophic scars by multiple needle punctures. Dermatol Surg. 2001;27:23.
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.    Marcus DV, Mahmoud BH, Hamzavi IH. Granuloma annulare treated with rifampin, ofloxacin, and minocycline combination therapy. Arch Dermatol. 2009;145:787–789.
18.    Baumann LS, Halem ML. Lip silicone granulomatous foreign body reaction treated with Aldara (imiquimod 5%). Dermatol Surg. 2003;29:429–432.
19.    Pasternack FR, Fox LP, Engler DE. Silicone granulomas treated with etanercept. Arch Dermatol. 2005;141:13–15.
20.    Desai AM, Browning J, Rosen T. Etanercept therapy for silicone granuloma. J Drugs Dermatol. 2006;5:894–896.

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