1. Aesthetic Surgery Journal
2014, Vol. 34(3) 394–399
© 2014 The American Society for
Aesthetic Plastic Surgery, Inc.
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DOI:10.1177/1090820X13520448
www.aestheticsurgeryjournal.com
Breast Surgery
Reduction mammaplasty is a procedure commonly per-
formed by plastic surgeons. The procedure usually results
in high satisfaction rates and low complication risks—the
most common being infection, hematoma, seroma, and
wound breakdown. Pyoderma gangrenosum (PG) is a rare
postoperative complication of breast surgery. We describe
a case of PG following unilateral breast reduction that
resulted in systemic inflammatory response; the patient’s
PG was resolved via treatment with prednisone and topical
tacrolimus. This case report highlights needed awareness
of both PG’s progression and its treatment, as a delayed
diagnosis may detrimentally affect patient care both
acutely and long-term. The consequences can include neg-
atively impacted cosmesis.
CASE PRESENTATION
A 61-year-old woman presented on September 12, 2011, for a
right reduction mammaplasty to achieve breast symmetry
(Figure 1). The patient had history of stage I breast cancer
and had undergone a left partial mastectomy with radiation 2
years prior. Her medical history was significant for epilepsy,
minor surgical procedures, and smoking; personal and family
histories were negative for autoimmune disorders. The
patient underwent right breast reduction mammaplasty with
a standard Wise-pattern incision to improve symmetry.
On the fourth day postoperatively, the patient returned
to the clinic and was found to have early postoperative
520448AESXXX10.1177/1090820X13520448Aesthetic Surgery JournalDoren and Aya-ay
research-article2014
Dr Doren is an Integrated Plastic Surgery Resident in the Department
of Surgery, Division of Plastic Surgery, University of South Florida,
Tampa, Florida. Dr Aya-ay is a plastic surgeon in private practice in
Lutz, Florida.
This article was reported in poster format at the Southeastern
Society of Plastic and Reconstructive Surgeons (SESPRS); June 1,
2013; Bonita Springs, Florida.
Corresponding Author:
Dr Melanie Lynn Aya-ay, 17523 North Dale Mabry Highway, Lutz,
FL 33548, USA.
E-mail: melanieayaaymd@yahoo.com
Pyoderma Gangrenosum Following Breast
Reduction: Treatment With Topical
Tacrolimus and Steroids
Erin Louise Doren, MD; and Melanie Lynn Aya-ay, MD
Abstract
Pyoderma gangrenosum (PG) is a rare, noninfectious, inflammatory dermatosis usually associated with autoimmune disorders. Wounds may mimic a
necrotizing infection, and the diagnosis is usually made after antibiotic therapy fails. Debridement may cause even larger wounds because of pathergy, so
PG treatment consists of corticosteroids and local wound care. Pyoderma gangrenosum can be a devastating complication of breast and aesthetic surgery.
We describe a case of PG following unilateral breast reduction that resulted in systemic inflammatory response; after treatment with prednisone and topical
tacrolimus, the PG was resolved. The application of topical tacrolimus may reduce the need for prolonged corticosteroids.
Level of Evidence: 5
Keywords
breast reduction, pyoderma gangrenosum, topical tacrolimus, necrotizing soft tissue infection, autoimmune, debridement
Accepted for publication July 18, 2013.
Case Report

2. Doren and Aya-ay 395
wound dehiscence and erythema. Located at the vertical
incision’s midpoint, the wound measured 3 × 1.5 cm. The
wound exhibited surrounding erythema and superficial
epidermolysis but no evidence of purulence, fluctuance, or
significant induration (Figure 2). The patient was started
on levofloxacin and given local wound care with silvadene
dressing changes for presumed cellulitis infection.
On day 8 postoperatively, the patient returned to the
clinic complaining of fever and a rapidly progressing
wound. The wound measured 25 × 15 cm and included
necrotic tissue, erythema, purple discoloration of skin
edges, an undermining violaceous border, and intense pain
at the wound site and surrounding tissue (Figure 3). The
patient was subsequently admitted to the hospital and
started on broad-spectrum intravenous (IV) antibiotics. An
infectious disease consult was requested. Blood, urine, and
wound cultures sent to the laboratory were negative. The
wound continued to progress rapidly despite antibiotic
therapy and local wound care.
On postoperative day 11, the patient was taken to the
operating room for necrotic tissue debridement. Following
this procedure, the patient developed systemic inflamma-
tory response syndrome (SIRS) characterized by hypoten-
sion, marginal urine output, leukocytosis, and fever (Figure
4). The patient was transferred to the intensive care unit
(ICU) and was started on a norepinephrine drip and fluid
resuscitation. All repeat cultures and debridement wound
cultures remained negative. The tissue specimen’s pathol-
ogy showed benign adipose tissue with severe acute necro-
tizing inflammation and abscess formation.
A diagnosis of PG with systemic inflammatory response
syndrome was suspected. High-dose IV steroids were initi-
ated on postoperative day 12: within 24 hours, wound
progression ceased, and the wound edges began to reepi-
thelialize (Figure 5). The patient was quickly weaned off
norepinephrine and became afebrile with an improved and
then normalized white blood cell count. The wound was
additionally treated with topical 0.1% tacrolimus; the IV
steroids were subsequently tapered. Wound healing pro-
gressed rapidly, and the patient was discharged on oral
prednisone taper and topical tacrolimus on postoperative
day 25 (Figure 6). Topical tacrolimus was started on post-
operative day 13 and stopped on postoperative day 45
(because systemic levels were high). Eight months postop-
eratively, the patient exhibited healed wounds and no
signs of continued inflammation or infection (Figure 7).
DISCUSSION
Pyoderma gangrenosum was first described in the medical
literature in 1930 with the report by Brunsting et al1
of 5
cases. It is defined as a rare, noninfectious, inflammatory
neutrophilic dermatosis of unknown origin. Presentation
typically begins with a pustule that spreads concentrically
to rapidly undermine healthy skin. Lesions then progress
to painful ulcerations with a central necrotic area and pur-
plish violaceous borders, surrounded by a margin of ery-
thema. Pyoderma gangrenosum is most commonly found
in the lower extremities but reportedly occurs at almost
any body site, including the upper extremity, trunk, breasts,
vulva, and head and neck.2-4
Pyoderma gangrenosum is usually associated with a
systemic disease process. The most common is inflamma-
tory bowel disease, including both Crohn disease and
ulcerative colitis. Other associated systemic diseases
include rheumatoid arthritis, hepatitis, thyroid disorders,
monoclonal gammopathy, myeloma, and malignancies.1,2
In this case, the patient had no known risk factors for PG.
Figure 1. This 61-year-old woman presented with breast
asymmetry after left breast partial mastectomy and radiation.
Figure 2. Four days after right breast reduction
mammaplasty with a standard Wise-pattern breast reduction
to improve symmetry, the patient’s vertical incision (3 ×
1.5-cm wound) exhibited surrounding erythema and
superficial epidermolysis.

3. 396 Aesthetic Surgery Journal 34(3)
During hospitalization, her sedimentation rate and
C-reactive protein were elevated, but her cortisol level,
antinuclear antibodies, and rheumatoid factor were nor-
mal. The patient did not undergo any additional testing to
identify predisposing conditions such as stool guaiac test,
free T4, free T3, thyroid-stimulating hormone, anti–thyroid
peroxidase, anti-thyroglobulin, anti–double-stranded DNA,
rapid plasma regain, hepatitis panel, or colon cancer
markers.5
The diagnosis of PG is based on both exclusion of other
disorders and prompt symptom resolution with steroid treat-
ment. Patients with PG are often initially misdiagnosed and
treated for a bacterial infection, since PG may be accompa-
nied by fever and erythema suggestive of cellulitis. When
antibiotic therapy fails or a wound persists despite local
care, a diagnosis of PG should be suspected. Diagnosis may
be aided by histological specimens that typically show
inflammatory infiltrate, endothelial swelling, necrosis, and
abscess formation in the dermis and fat.2
Our patient’s PG diagnosis was delayed, since she was
initially treated for early incisional breakdown and infec-
tion from ischemic necrosis, attributed to her smoking his-
tory. The clinical characteristic that later distinguished the
PG diagnosis was the early pustule-like appearance that
Figure 3. (A) On postoperative day 8, the patient presented with rapid wound progression extending above the nipple of her
right breast, with necrotic tissue, erythema, and intense pain. The wound measured 25 × 15 cm. (B) This view shows the
disease progression’s full extent.
Figure 4. The right breast’s appearance is shown
immediately after surgical debridement in the operating
room on postoperative day 11.
Figure 5. Within 24 hours of treatment with intravenous
steroids, following pyoderma gangrenosum diagnosis, on
postoperative day 13, the wound’s progression has ceased,
and its edges have begun to reepithelialize.

4. Doren and Aya-ay 397
spread rapidly and concentrically to involve the skin flaps
and tissue above the nipple-areolar complex (NAC) as
well. Compared with necrotizing fasciitis, PG wounds
mainly involve skin and subcutaneous fat; they do not fol-
low fascial planes or display crepitus. In addition, the dis-
ease process spared the NAC, which is a commonly
described feature of PG of the breast.5-16
Another particularly important aspect of PG is that cuta-
neous wounds will often intensify by pathergy from surgical
debridement.17
In the case of cellulitis or abscess, initiating
a course of antibiotics and surgical debridement will usually
resolve or at least improve the clinical condition. The devel-
opment of PG also may be caused by surgical procedures.
Pyoderma gangrenosum has been documented to occur
after procedures such as chest tube placement, laparoscopy,
facelift, hip replacement, minor trauma, and cuts or needle
sticks.6,18-22
Pyoderma gangrenosum after elective breast or
cosmetic surgery can be particularly devastating. Although
rare, case reports show PG occurring spontaneously in the
breast5
and after trauma,6
breast reconstruction,23
masto-
pexy,7-8
mastectomy,4
and reduction mammaplasty.9-16
Wollina et al24
suggested that areas rich in subcutaneous fat
may have a higher risk of pyoderma—thus contributing to
PG incidence after breast surgery. We believe surgery was
our patient’s only risk factor for the development of PG; no
other aspects of the patient’s history or routine care can
explain PG occurrence.
Although much controversy remains concerning the
most effective treatment plan for PG, managing the condi-
tion typically includes local wound care and systemic ste-
roids. Prednisone, cyclosporine A, dapsone, sulfa drugs, oral
tacrolimus, methotrexate, tumor necrosis factor–α blockers,
hyperbaric oxygen, and skin grafting have all been variably
successful.3,24-27
In most cases, initial treatment starts with
prednisone 1 to 2 mg/kg/d to halt necrotic progress.27
If an
associated systemic disease is present, complete and sus-
tained resolution of the lesions occurs when the disease is
treated, such as in patients with ulcerative colitis cured by
proctocolectomy.1,2
The best way to assess wound improve-
ment is with serial observation, wound measurements, and
photography. Healing begins with epithelialization from the
wound’s edges. When the erythematous and indurated bor-
ders begin to flatten and pain decreases, anti-inflammatory
medications can be tapered.27
Novel treatments for PG of the breast have been
described and include treatment with Integra Dermal
Regeneration Template (Integra, Plainsboro, New Jersey)7,10
and skin grafting after allograft application and immuno-
suppressive therapy.28
The literature suggests debridement
and skin grafting after proper systemic treatment is safe
and can yield improved results.29,30
Synergistic treatments,
including debridement, vacuum-assisted closure, and
hyperbaric oxygen, have also been suggested.31
This case of PG after breast reduction was particularly
devastating, in that the patient was admitted to the ICU
and needed pressor support to maintain adequate end-
organ perfusion secondary to SIRS. We believe this may
have resulted from the delayed treatment, since the patient
did not return to the clinic after her initial visit on postop-
erative day 4 until postoperative day 8; between visits, she
experienced increasing pain, fever, and a rapidly progress-
ing wound. The factors assisting in this patient’s success-
ful case management included an early infectious disease
Figure 6. The patient’s right breast is shown at the time of
discharge on postoperative day 25.
Figure 7. Eight months postoperatively, after treatment
with IV steroids followed by topical tacrolimus, the patient’s
wound has healed, with no signs of inflammation or
infection.

5. 398 Aesthetic Surgery Journal 34(3)
consultation, consultation with senior surgeons, and use
of IV steroids in conjunction with topical 0.1% tacrolimus.
We chose dual therapy of steroids and topical tacrolimus
based on reports in the literature suggesting the effective-
ness of tacrolimus in autoimmune dermatoses.
Tacrolimus is an immunomodulator that works by
inhibiting T-lymphocyte activation. It is more commonly
used for the topical treatment of atopic dermatitis.32
The
ointment comes in concentrations of 0.03% or 0.1% and is
generally applied as a thin layer twice daily, left open to air
or covered with a simple gauze dressing. The approximate
retail price for a 0.1% 60-g tube is $370. Common side
effects include burning sensation, pruritus, and the poten-
tial for herpes simplex virus breakout.32
Unlike topical ste-
roids, tacrolimus does not cause skin atrophy. Adverse
effects of systemic tacrolimus include nephrotoxicity, neu-
rotoxicity, and hypertension. Metabolized by the liver,
tacrolimus has been shown to have a 7 times greater
absorption rate when applied to damaged versus intact
skin.33
Therefore, we believe it necessary to measure
whole-blood levels of tacrolimus during treatment of open
wounds.34
The therapeutic range for oral tacrolimus in
renal transplant patients is documented at 5 to 15 ng/mL;
adverse effects are usually seen when levels are greater
than 15 ng/mL.35
A period of 2.5 days after the initiation of
therapy should elapse before the first whole-blood level is
drawn; however, no defined period of continued monitor-
ing is yet established for topical tacrolimus therapy.35
While oral tacrolimus is an established treatment option
for PG, few studies have documented treatment with topi-
cal use of tacrolimus, and to our knowledge, no studies
document tacrolimus applied to the breast. One case
report, in which tacrolimus ointment was applied daily for
4 weeks, showed ulcers healing after 1 week and resolu-
tion after 5 weeks.34
A study of 5 patients, all treated with
tacrolimus alone, showed complete resolution in 4 to 8
weeks.36
Pitarch et al34
showed that tacrolimus reached
systemic range for immunosuppression at 12 days, while
other studies have shown low systemic levels of tacrolimus
throughout the course of treatment.36,37
The initial sys-
temic tacrolimus levels for our patient were low, but after
30 days of treatment, levels were greater than 30 ng/mL.
Treatment was discontinued and silvadene applied until
wounds completely epithelialized. Four days after discon-
tinuation of tacrolimus, systemic levels were again low.
Our patient did not display any side effects from the medi-
cation. We believe the application of this topical immuno-
modulator allowed for earlier epithelialization and may
have allowed for sooner tapering of the systemic steroids
to a lower dose, as the IV steroids were immediately
tapered down to 5 mg orally at the time of discharge.
Randomized controlled studies investigating the use of
monotherapy topical tacrolimus compared with oral/IV
steroids are necessary to determine if treatment time is sig-
nificantly shortened.
CONCLUSIONS
This article reports on a rare finding of breast PG after
reduction mammaplasty in a patient without history of
systemic disease or risk factors. Pyoderma gangrenosum
can be life-threatening and certainly is devastating to
the cosmetic patient. Early clinical suspicion is key to
successful treatment. Surgeons must be aware of poten-
tial PG development in patients and be familiar with its
clinical presentation. We also recommend early infec-
tious disease and dermatology consultations for assis-
tance in the diagnosis and management of this rare
disease process. Through a team approach for this
patient’s case, we chose treatment with topical tacroli-
mus, which was an effective adjuvant to systemic ste-
roids. In the future, we will consider topical tacrolimus
monotherapy for isolated cases of PG not associated
with any known systemic disorder.
Acknowledgments
We thank Dr Dennis Hammond for his knowledge and assis-
tance in successfully managing this patient and her treatment.
We also thank Dr Yvonne Pierpont for her editing expertise.
Disclosures
The authors declared no potential conflicts of interest with
respect to the research, authorship, and publication of this
article.
Funding
The authors received no financial support for the research,
authorship, and publication of this article.
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