INTRODUCTION: Pyoderma gangrenosum (PG) is a rare sterile neutrophilic dermatosis characterized by painful recurrent ulcerations. It is frequently associated with inflammatory bowel disease, rheumatoid arthritis, or malignancies. PG is a diagnosis of exclusion, and it is based on clinical presentation, histology, history of an underlying disease, and exclusion of other causes of ulceration. CASE REPORT: The authors report a 62-year-old male who developed a nonhealing ulcer at the site of incision following nephrectomy for renal cell carcinoma. Past medical history included chronic lymphocytic leukemia treated with rituximab. Histology of the skin lesion showed a phlegmonous nonspecific inflammation without being able to differentiate between a necrotizing wound infection and PG. The patient’s condition was initially diagnosed as an infectious process and treated accordingly. After unsuccessful results with systemic antibiotics, high-dose corticosteroids induced prompt healing of the wound. On these bases, the diagnosis of postoperative PG within chronic lymphocytic leukemia and renal cell carcinoma was made. CONCLUSION: Faced with postoperative necrotizing ulceration resistant to correctly administered antibiotics, PG must be considered. In such condition, the diagnosis must not be guided primarily by histology and early advice of a dermatologist is recommended

Caius Solovan

Claudia Wickenhauser

Elena Chiticariu

Robert Smiszek

Infectious Diseases and Therapy

PubMed

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Postoperative Pyoderma Gangrenosum in Association with Renal Cell Carcinoma and Chronic Lymphocytic Leukemia

CASE REPORT
Postoperative Pyoderma Gangrenosum in Association
with Renal Cell Carcinoma and Chronic Lymphocytic
Leukemia
Caius Solovan • Robert Smiszek •
Claudia Wickenhauser • Elena Chiticariu
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Received: April 15, 2013 / Published online: June 11, 2013
 The Author(s) 2013. This article is published with open access at Springerlink.com
ABSTRACT
Introduction: Pyoderma gangrenosum (PG)
is a rare sterile neutrophilic dermatosis
characterized by painful recurrent ulcerations.
It is frequently associated with inflammatory
bowel disease, rheumatoid arthritis, or
malignancies. PG is a diagnosis of exclusion,
and it is based on clinical presentation,
histology, history of an underlying disease,
and exclusion of other causes of ulceration.
Case Report: The authors report a 62-year-old
male who developed a nonhealing ulcer at the
site of incision following nephrectomy for renal
cell carcinoma. Past medical history included
chronic lymphocytic leukemia treated with
rituximab. Histology of the skin lesion showed a
phlegmonous nonspecific inflammation without
being able to differentiate between a necrotizing
wound infection and PG. The patient’s condition
was initially diagnosed as an infectious process
and treated accordingly. After unsuccessful
results with systemic antibiotics, high-dose
corticosteroids induced prompt healing of the
wound. On these bases, the diagnosis of
postoperative PG within chronic lymphocytic
leukemia and renal cell carcinoma was made.
Conclusion: Faced with postoperative
necrotizing ulceration resistant to correctly
administered antibiotics, PG must be
considered. In such condition, the diagnosis
must not be guided primarily by histology and
early advice of a dermatologist is recommended.
Keywords: Chronic lymphocytic leukemia;
Infectious diseases; Neutrophilic dermatosis;
Pyoderma gangrenosum; Renal cell carcinoma;
Ulceration
C. Solovan  E. Chiticariu (&)
Dermatology Department, University of Medicine
and Pharmacy ‘‘Victor Babes’’, Timisoara Romania,
Marasesti 5, 300077 Timisoara, Romania
e-mail: elena.chiticariu@yahoo.com
R. Smiszek
Urology Department, Helios Kliniken Leipziger
Land, Borna, Germany
C. Wickenhauser
Institute of Pathology, University of Leipzig,
Leipzig, Germany
Enhanced content for this article is
available on the journal web site:
www.infectiousdiseases-open.com
123
Infect Dis Ther (2013) 2:75–80
DOI 10.1007/s40121-013-0008-4
INTRODUCTION
Pyoderma gangrenosum (PG) is a rare sterile
inflammatory neutrophilic dermatosis
characterized by recurrent painful ulcerations.
Although the etiology is unclear, it is often
associated with inflammatory bowel disease,
rheumatoid arthritis or malignancies [1].
Recently, this condition was included in the
group of cutaneous autoinflammatory disorders,
characterized by defects in the innate immune
response [2]. The name suggests an infectious
agent but autoimmune mechanisms, neutrophil
dysfunction, and disturbance of cellular immunity
seem to be implicated. The accumulation of
neutrophils in the skin lesions, similar with Sweet
syndrome (acute febrile neutrophilic dermatosis)
supporting the inclusion of PG within the
spectrum of neutrophilic dermatoses [3]. The
frequency of pathergy (development of new
lesions or aggravation of existing ones following
local injuries) suggests altered inflammatory
responses to nonspecific stimuli. The widely
accepted hypothesis is that PG has a complex and
multifactorial pathogenesis, including genetic
predisposition, paraneoplastic or para-immune
phenomena, and undefined infectious agents
[4, 5].
The most common clinical classification
includes four major types: ulcerative, pustular,
bullous, and vegetative [6, 7]. Other particular
forms have also been described: peristomal,
genital, mucosal, extracutaneous, and
postoperative [8–11]. Herein, the authors
present a patient with postoperative PG in
association with renal cell carcinoma and
chronic lymphocytic leukemia.
CASE REPORT
A 62-year-old male patient presented with renal
carcinoma. The tumor was removed by partial
nephrectomy in cold ischemia without
undesirable events. Histology confirmed a
well-differentiated renal cell carcinoma with
histologically negative margins. The patient
also suffered from stable chronic lymphocytic
leukemia treated with rituximab and
hypothyroidism under substitution with
L-thyroxine.
Five days after nephrectomy, a progressive
painful ulceration developed rapidly at the site
of incision. The lesion was deep and had an
overhanging violaceous border. The left lumbar
area was indurated and erythematous (Fig. 1a).
The patient became febrile and his white
blood cells (WBC) rose from 6,100 to 56,000/
Fig. 1 Pyoderma gangrenosum: a extensive ulceration at
the site of incision with violaceous borders at the
periphery; b the ulceration after 12 days of corticotherapy
76 Infect Dis Ther (2013) 2:75–80
123
mm3. C-reactive protein (CRP) levels increased
from 1.4 to 259 mg/L. At this point, a wound
infection was suspected. He was empirically
treated with antibiotics (ciprofloxacin, then
imipenem and doxycycline) but its condition
progressed relentlessly. Ultrasound and
computer tomography scans failed to identify
an abscess. Surgical wound revision did not
identify any sign of bacterial infection.
Preoperative, intraoperative, and postoperative
wound culture remained negative. However,
blood culture was positive for Staphylococcus
haemolyticus, and imipenem was changed
for vancomycin. Despite broad-spectrum
antibiotics, there was a sustained expansion of
the skin lesion. PG was suspected and the
patient was referred to a dermatologist.
A biopsy specimen of the edge of the
ulceration showed a phlegmonous nonspecific
inflammation without being able to
differentiate between a necrotizing wound
infection and PG. Microbiology of the skin
specimen was negative. Periodic acid schiff
(PAS) staining was negative for fungal
infection. There were no signs of vasculitis or
malignancy. A second skin biopsy was
performed. Histology showed a chronic
granulomatous inflammation with
subepithelial edema. A minimal focal
inflammatory reaction affecting small and
medium-sized vessels was identified in
hypoderm (Fig. 2). Myeloperoxidase (MPOX)
staining was positive (Fig. 3). CD79a (Fig. 4)
and Epstein–Barr virus latent membrane
protein-1 oncogene (EBV-LMP) were negative.
Taking into account the medical history,
clinical features, histology, and lack of
pathogens, the diagnosis of postoperative PG
within chronic lymphocytic leukemia and
renal cell carcinoma was made. The diagnosis
of bacteremia with S. haemolyticus was also
made.
Therapy with high-dose prednisolone
(250 mg/day) was initiated. The prednisolone
therapy was gradually reduced and stopped
after 3 weeks. Standard wound care consisted
of polyhexanide applications and enzymatic
debridement of necrotic tissue. After 2 weeks
of treatment, WBC decreased to 6,000/mm3 and
CRP to 47 mg/L. The corticosteroids induced
prompt healing of the wound (Fig. 1b).
Fig. 2 Histology: haematoxylin and eosin staining of the
vital edge of the dermal debridement with pronounced
phlegmonous and granulomatous nonspeciﬁc inﬂammation
approximating the deep dermis and the subcutaneous fat
tissue
Fig. 3 Immunohistochemistry: the inﬂammatory inﬁltrate
mostly consisted of myeloperoxidase positive granulocytes
with only few concomitant lymphocytes
Infect Dis Ther (2013) 2:75–80 77
123
Informed consent was obtained from the
patient for being included in the study.
DISCUSSION
Postoperative PG was first described by Cullen
in 1924 [12]; therefore, it is also known as
postoperative progressive gangrene of Cullen.
This entity is considered today as a variant of
PG, similar to classical ulcerative form [13]. This
form of PG begins as multiple small ulcerations
several days to weeks after apparently normal
healing [14]. It has been reported most often in
association with abdominal and breast surgery,
but it can complicate any invasive procedure
[15]. Typical presentation is a primarily sterile
ulcer several days after surgery, with rapid
progression, lack of response to antibiotics and
removal of necrotic tissue, and prompt healing
after immunosuppressive agents [13].
This case is an excellent example of
postoperative PG affecting a patient with two
different types of malignancies simultaneously.
The PG lesions have been initiated by surgical
procedure, but the patient’s status clearly
played a significant etiopathogenetic role. The
frequency of association between PG and
malignancies is approximately 7% (in
particular leukemia) [16]. More than half of all
reported patients with PG in association with
leukemia, presented acute myeloblastic
leukemia with granulocytic maturation (M2),
but chronic lymphocytic leukemia was also
identified [17, 18]. To the author’s knowledge,
PG was not reported in association with renal
cell carcinoma, but it was reported in another
patient receiving maintenance rituximab
therapy for lymphoma [19].
The diagnosis of PG can be difficult. It
depends upon a combination of clinical
presentation, histology, history of underlying
diseases, and exclusion of other conditions.
Given the nonspecific histological findings
and a positive blood culture for S.
haemolyticus, it was very difficult to exclude a
necrotizing wound infection. The leukocytosis
in the absence of lymphocytosis cannot be
explained by chronic lymphocytic leukemia or
bacteremia. Cases of postoperative PG with
leukaemoid reaction (WBC [50,000/mm3) in
the absence of hematologic malignancies have
been reported [20, 21]. Despite a positive blood
culture, the wound culture remained negative
and the skin lesion responded to corticosteroids
instead of antibiotics.
Similar features can be found in Fournier’s
gangrene, a rare but life threatening disease
affecting patients with comorbidities, especially
diabetes mellitus and alcoholism. It is a
fulminant form of infective necrotising
fasciitis affecting the perineal, genital, or
perianal regions [22]. Wound culture is
commonly positive for at least three
organisms, including aerobes and anaerobes
[23]. Fournier’s gangrene requires an aggressive
approach, including broad spectrum
antibiotics, hemodynamic stabilization, and
surgical debridement. It was highlighted that
early surgical debridement is the first
Fig. 4 Immunohistochemistry: no indication of an
appreciable CD79a positive B-lymphoid cell population
78 Infect Dis Ther (2013) 2:75–80
123
therapeutic intervention and has a major
impact on the prognosis [24]. In contrast,
surgical intervention can aggravate PG due to
the pathergy phenomenon [25]. Other diseases
to be considered in the differential diagnosis are
malignancy, vasculitis, Sweet syndrome, or
factitious ulcerations [1].
CONCLUSION
In conclusion, faced with postoperative
necrotizing ulceration resistant to correctly
administered antibiotics, PG must be
considered in any case of apparently delayed
wound healing. Since the most important
findings suggestive for PG are painful ulcers
with rapid outgrowth and undermined,
violaceous borders in absence of infection, the
diagnosis must not be guided primarily by
histology and early advice of a dermatologist
is recommended.
ACKNOWLEDGMENTS
This work was not supported financially or
otherwise. Dr. Chiticariu is the guarantor for
this article, and takes responsibility for the
integrity of the work as a whole.
Conflict of interest. Dr. Solovan, Dr.
Smiszek, Dr. Wickenhauser, and Dr. Chiticariu
declare no conflict of interest.
Compliance with ethics guidelines. Informed
consent was obtained from the patient for being
included in the study.
Open Access. This article is distributed
under the terms of the Creative Commons
Attribution Noncommercial License which
permits any noncommercial use, distribution,
and reproduction in any medium, provided the
original author(s) and the source are credited.
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Postoperative Pyoderma Gangrenosum in Association with Renal Cell Carcinoma and Chronic Lymphocytic Leukemia

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