Silicone granuloma of the face treated with

minocycline
Meral J. Arin, MD, Jens Ba te, MD, Thomas Krieg, MD, and Nicolas Hunzelmann, MD
Cologne, Germany
Siliconoma represents a granulomatous foreign body reaction to silicone, which is often used for soft tissue
augmentation. Although considered as biologically inert for a long time, silicone has been implicated in
various undesirable local and systemic reactions, sometimes with a latency period of up to several decades.
Treatment of siliconomas is difcult and granulomas involving the face are a therapeutic challenge. We
present a 43-year-old woman with a severely disguring facial silicone granuloma who was successfully
treated with minocycline. ( J Am Acad Dermatol 2005;52:S53-6.)
V
arious injectable materials have been used for
cosmetic soft tissue augmentation including
silicone, collagen, hyaluronic acid, and min-
eral oil.
1
Silicone is a polymer of chemically related
organosilicon compounds of which polydimeth-
ylsiloxane (silicone oil) is the most widely used.
It has been shown that silicone polymers con-
tain multiple contaminants including fumed silica,
platinum, and low molecular weight polymers.
2
The
advantage of silicone is the biologic stability over
long periods of time compared to collagen and
hyaluronic acid, which are eventually resolved.
Following intradermal or subcutaneous injection,
silicon is deposited as droplets in the extracellular
matrix. A transient acute inammatory reaction may
follow, and at a later stage, the silicon droplets are
xed in the tissue upon development of surrounding
brous capsules. Silicone granulomas may develop
with a latency period of up to several decades
3
and
a variety of connective tissue disorders including
progressive systemic sclerosis, lupus erythematosus,
and rheumatoid arthritis have been attributed to
silicone.
4
However, a definite association could not
be established.
5
Systemic distribution of silicone can
cause granulomatous hepatitis, pneumonitis, and
death.
6
Clinically, silicone granuloma may present
as diffuse swelling and redness, subcutaneous
nodules, and in some cases, palpable adenopathy.
The differential diagnosis includes granulomas in
sarcoidosis, tuberculosis and rheumatoid arthritis,
lupus profundus, pseudolymphoma, and foreign
body granuloma of various origin. Treatment options
are limited and include surgical excision, cortico-
steroids, retinoids, and antibiotics.
We describe a case of a seriously disguring
silicone granuloma of the face following silicone
injection for facial soft tissue augmentation that was
successfully treated with minocycline.
CASE REPORT
A 43-year-old woman presented to our depart-
ment with facial swelling which was most pro-
nounced around the left eye and the upper lip.
Small erythematous nodules were noted at the upper
aspect of the left eye and at the root of the nose. The
swelling and the nodules progressed and became
most pronounced at the left upper eye lid, the upper
lip, and the nose. A thorough examination of the
patients history revealed injections of silicone for
cosmetic nasal augmentation 18 months earlier. The
exact composition of the injection solution was not
available, but was thought to contain collagen and
silicone. The severe disgurement had caused de-
pressive episodes, and the patient had been off paid
work as a nurse in elder care for several months.
On physical examination, several rm, well de-
marcated subcutaneous nodules with overlying ery-
thema were palpated on the upper part of the nose,
the upper lip, and at the upper aspects of both
eyelids. The biggest nodule, located at the left upper
eyelid, was several centimeters in size. A diffuse
swelling was noted that was most pronounced
around both eyes (Fig 1, A). There was no palpable
lymphadenopathy and the rest of the clinical exam-
ination was normal. Complete blood cell count as
This supplement is made possible through the
generous support of Stiefel Laboratories for the
American Academy of Dermatology.
From the Department of Dermatology, University of Cologne.
Funding sources: None.
Conflicts of interest: None identified.
Reprint requests: Meral J. Arin, MD, Department of Dermatology,
University of Cologne, 50924 Cologne, Germany. E-mail:
meral.arin@medizin.uni-koeln.de.
0190-9622/$30.00
2005 by the American Academy of Dermatology, Inc.
doi:10.1016/j.jaad.2004.07.014
S53
well as blood chemistry were within normal limits.
Measurement of angiotensin-converting enzyme and
soluble interleukin-2 receptor in the serum was
performed without any abnormal finding. A chest
radiograph revealed an induration at both recessus
costodiaphragmalis. No granulomas or bihilar
lymphadenopathy was noted.
An excisional skin biopsy was taken from the left
upper eye lidandrevealednumerous swiss cheese-
like cystic spaces of varying sizes throughout all
levels of the dermis compatible with silicone
vacuoles (Fig 1, C ). They were surrounded by
granulomas composed of multinucleated giant cells
and Langerhans cells that infiltrated into the muscle
layer. A diagnosis of silicone granuloma was
established and a treatment with minocycline (100
mg per day) was initiated since the patient had
previously developed glucose intolerance upon
short-term low dose (5-20 mg per day) oral prednis-
olone. Since the lesions were distributed extensively
over her face, surgical excision was not a good
option. Within 4 weeks of treatment, the swelling
and erythema improved substantially. During the
following weeks, the nodules became softer and
smaller; however, small nodules around the left eye-
lid were still visible. Minocycline was continued and
a follow-up visit 4 months after initiation of therapy
showed a significant clinical improvement (Fig 1, B).
Minocycline was continued for 6 months, and 1 year
after initiationof minocycline, the patient s condition
was still improving, showing an excellent regression
of induration and erythema. With improvement of
the cosmetic appearance, the patient was able to
work again and she re-engaged in social activity.
After initiation of treatment, the patient com-
plained of nausea. Since food has not been re-
ported to alter the absorption of minocycline, the
drug was administered after a meal, which led
to improvement of the gastrointestinal symptoms.
Progression of roughly symmetric brown macules
(melasma) on the malar aspects of the face was
noted during therapy. The extent of the contribution
of the patients co-medication (estradiol and le-
vonorgestrel) remains unclear. Rigorous photopro-
tection including sunscreen with an SPF of 60 and
avoidance of excessive sun exposure prevented
further accentuation of the hyperpigmentation.
DISCUSSION
Silicone granuloma is a severe granulomatous
tissue reaction following injection or implantation
of silicone. Clinically, it can present as cellulitis with
nodule formation, ulceration, skin induration, and
local lymph duct and lymph node enlargement.
Silicone can be identied and quantitated in the skin
by electron spectroscopy for chemical analysis,
which allows detection of even small amounts in
tissues.
7
Migration of the injected material to distant
locations, so-called metastasis, has been reported
and was also noted in our patient. We think that the
nodules around the eyes and the upper lip are the
result of migrated particles from the injection site at
the root of the nose. The time between injection and
onset of cutaneous symptoms can vary from a few
months to several years.
3,8
In our patient, the
symptoms started 7 months after silicone injection.
The pathogenesis of granuloma formation is still
unknown. Biologic substances such as collagen are
phagocytized by macrophages within 1 to 3 months
after implantation and will be replaced by broblasts
and collagen bers.
9
Phagocytosis has so far been
described for particles with a size of up to 15 m,
10
but can also occur in the case of silicone that has
Fig 1. a, Firm erythematous nodules and facial swelling
18 months after silicone injection for soft tissue augmen-
tation, and (b) 4 months after treatment with minocycline.
Note resolution of the biggest nodule at the left upper
eyelid and regression of the erythematous indurated
edema of the face. c, Clear vacuoles of varying sizes
compatible with former deposits of silicone. Arrow:
multinucleated giant cell. (c, Hematoxylin-eosin stain;
original magnification: c, 3 40).
J AM ACAD DERMATOL
FEBRUARY 2005
S54 Arin et al
a mean diameter of 170 m.
11
In vitro, silicone
polymers have been shown to elicit a significant
change in the cellular configuration and a progres-
sive reduction in proliferation of dermal fibro-
blasts.
12
In a rat model, injection of silicone caused
an inflammatory response with fibroblasts, macro-
phages, and lymphocytes around the sites of im-
plantation. The intensity of the cellular and capsular
response was lowest for silicone oil; fumed silica
elicited the most highly reactive response.
13
Interestingly, secreted protein, acidic and rich in
cysteine (SPARC), a matricellular glycoprotein that
modulates the interaction of cells with the extracel-
lular matrix, has been implicated as an important
modulator of encapsulation of implanted biomate-
rial.
14
In mice lacking SPARC, a significant decrease
in capsular thickness around implanted poly-
dimethylsiloxane disks was noted compared to
wild-type mice, indicative of a diminished foreign
body reaction. In contrary, mice lacking throm-
bospondin 2 (TSP2), another protein that modulates
cell-matrix interaction, show an enhanced foreign
body reaction with formation of highly vascularized
capsules around implanted polydimethylsiloxane
disks supporting the role for TSP2 as a physiologic
inhibitor of angiogenesis.
15
These findings implicate
an important role of the extracellular matrix in the
regulation of foreign body reactions.
Treatment of silicone granuloma is difcult and
various regimes have been used. Surgical excision
has been suggested when possible; however, total
removement may not be possible or may require
extensive debridement when silicone migrates to
distant areas. Moreover, the cosmetic result may not
be satisfactory and is hardly predictable before
surgery. The large extent of involvement in our
patient with nodules on both eyelids, nose, and
upper lip precluded surgical removal. Since the
nodules were located deep in the dermis, topical
treatment was not considered. Injection of steroids or
treatment with oral steroids may have a temporary
benecial effect; however, a relapse is often seen
when the dose is tapered.
16
Complete resolution of
silicon granulomas on the face has been reported
following treatment with low dose retinoids (iso-
tretinoin 20 mg per day) over 6 months.
16
Various
cytokines have been implicated in granulomatous
conditions and tumor necrosis factor (TNF)ea is
thought to play a primary role.
17
Pentoxifylline,
which decreases TNF-a production from macro-
phages, has been used in a few cases of sar-
coid granulomas and silicone granulomas, with
variable results.
18,19
Recently, successful treatment
with allopurinol of foreign body granulomas caused
by a mixture of polymethylmethacrylate and colla-
gen has been reported.
9
Treatment over 24 weeks
resulted in almost complete regression of the cuta-
neous symptoms. Allopurinol is thought to act as
a catalyst in the formation of superoxides or as
a scavenger of free radicals, which may play a role in
the pathogenesis of granulomatous diseases. The
exact mode of action remains to be elucidated.
The rationale for administration of minocycline in
granulomatous tissue reactions is its anti-inamma-
tory, immunomodulating, and anti-granulomatous
effect.
20-21
In previous reports describing mino-
cycline in the treatment of silicone granuloma,
minocycline was administered in a higher dose
(100 mg twice daily) either as monotherapy or in
combination with oral prednisone.
22
Improvement
of the condition was noted within several weeks;
however, the follow-up period of up to 4 months is
still short. In a patient in whom breast-injected
silicone was delivered to multiple body sites, in-
cluding the face, minocycline treatment (100 mg
once daily) resulted in improvement of the condi-
tion; however, specific information and follow-up
are not available.
23
We report the succesful treatment of severe
disguring facial silicone granuloma with a low dose
minocycline regime (100 mg once daily). Clinical
improvement was noticed 4 weeks after initiation of
treatment, and signicant regression of the nodules
and the inammatory response was seen after
4 months. Minocycline was administered for 10
months and a follow-upof the patient after more than
1 year after initiation of therapy showed excellent
clinical improvement. Compared to previous re-
ports, minocycline (100 mg once daily) as a mono-
therapy was as effective as oral prednisone or
a combination of oral prednisone and minocycline
(100 mg twice daily). Side effects, such as pigmen-
tation, were minimal and were well tolerated. Our
data highlight the prolonged course of the disease,
which sometimes necessitates a long duration of
treatment. In our opinion, minocycline monotherapy
represents a useful treatment option, especially for
silicone granuloma of the face.
We thank Professor G. Mahrle for valuable comments
on the manuscript.
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