Download Infliximab for Treatment of Pyoderma Gangrenosum Associated with

Pyoderma gangrenosum in Crohn’s disease
Infliximab for Treatment of Pyoderma Gangrenosum Associated
with Clinically Inactive Crohn’s Disease. A Case Report
George Kouklakis1,2, John Moschos1,3, Grigoris I. Leontiadis3, Savvas Kadis3, Alexandros Mpoumponaris1,
Epaminondas Molyvas1, George I. Minopoulos2
1) 424 General Army Hospital, Thessaloniki. 2) Medical School Democritus University of Thrace, Alexandroupolis,
Greece. 3) Queen Elizabeth Hospital, Gateshead, UK
Abstract
We report the case of a 57-year old female patient with
refractory to treatment pyoderma gangrenosum associated
with clinically inactive Crohn’s disease. Pyoderma
gangrenosum was successfully treated with Infliximab, a
chimeric monoclonal antibody that inhibits tumour necrosis
factor alpha (TNF-α). Our case report suggests that
Infliximab, a therapeutic agent for refractory and fistulizing
Crohn’s disease, may also be safe and effective in the
treatment of Crohn’s disease associated pyoderma
gangrenosum, even though the inflammatory bowel disease
is clinically inactive and repeated infusions may be required
for successful treatment.
Key words
Crohn’s disease - pyoderma gangrenosum - Infliximab
Rezumat
Prezentãm cazul unei femei de 57 de ani cu pyoderma
gangrenosum refractar la tratament, asociat cu boalã Crohn
clinic inactivã. Pyoderma gangrenosum a rãspuns la
administrarea de Infliximab, anticorp monoclonal chimeric
care inhibã factorul de necrozã tumoralã alfa (TNF-α). Acest
caz sugereazã cã Infliximab, administrat în boala Crohn
refractarã ºi complicatã cu fistule, poate fi eficace ºi sigur în
boala Crohn asociatã cu pyoderma gangrenosum, chiar dacã
boala inflamatorie intestinalã este asimptomaticã. Pentru
succesul terapeutic pot fi necesare mai multe administrãri.
bowel disease (IBD). The treatment of PG is rather empirical
and is based on clinical experience. It includes local therapies
and immuno-modulating agents. Infliximab (Remicade ®), a
chimeric monoclonal antibody that inhibits tumour necrosis
factor alpha (TNF-α), has been successfully used to treat
patients with moderate to severe and fistulizing Crohn’s
disease (CD) (1). Several case reports and retrospective
reviews of case series suggest that Infliximab may induce
healing of PG lesions in patients with IBD.
We present a female patient with quiescent CD involving
the small intestine that developed refractory PG, but
responded favourably to treatment with Infliximab.
Case report
A 57-year-old female patient was referred to our outpatient clinic by a dermatologist. She had a large lesion of
about 5 cm in diameter on her left lower extremity, diagnosed
to be PG (Fig.1). The patient did not report previous trauma
to the site of the lesion. The lesion had been refractory to
local treatment, corticosteroids and azathioprine. She had a
history of several episodes of bloody diarrhoea in the past,
for which she had not sought medical advice.
Introduction
Pyoderma gangrenosum (PG) is an inflammatory
exulcerative skin lesion that may complicate inflammatory
Romanian Journal of Gastroenterology
December 2005 Vol.14 No.4, 401-403
Address for correspondence: John Moschos MD PhD
Papadimitriou 10
55131, Kalamaria, Greece
Email: [email protected]
Fig.1 Pyoderma gangrenosum, associated with clinically inactive
Crohn’s disease.
402
She had a normal colonoscopy but the terminal ileum
biopsies were diagnostic of Crohn’s disease.
The patient received three i.v. infusions of Infliximab at
a dose of 5 mg/kg at 0, 2 and 8 weeks, respectively. Infliximab
was administered solely for the PG lesion since she had no
active or fistulizing CD. The patient was able to taper off
corticosteroids completely and thereafter did not require
additional corticosteroid treatment. Infliximab was well
tolerated with no adverse effects. Following the first infusion
there were signs of improvement and after the third infusion
the lesion healed completely. After one year, the lesion
remains completely healed.
Discussion
Pyoderma gangrenosum (PG) is an inflammatory
condition that is characterized by development of chronic
ulcerative skin lesions preferentially on the lower extremities.
About 36-50% of patients with PG have IBD. Conversely,
PG occurs in about 1-2% of patients with IBD and may bear
no relation to the clinical activity of the intestinal disease as
in our patient, in whom the IBD was clinically inactive (2) .
However, clinical experience implies that PG associated with
CD heralds active intestinal inflammation, even if symptoms
of the gut are not overt initially (3).
The pathogenesis of PG is unknown. It is suggested
that an aberrant immune system is central to the
pathogenesis of this disease and thus, effective long term
management of PG will involve sustained control of systemic
and local inflammation by alteration of the immune system.
PG treatment includes local wound care in conjunction
with systemic treatment with immunomodulating agents.
Local therapies comprise topical pharmacological treatment,
dressings and intralesional injection of corticosteroids or
cyclosporine. Systemic immuno-modulating agents include
corticosteroids, azathioprine, 6-MP, alkylating agents and
cyclosporine. The high doses of corticosteroids needed to
treat PG have been associated with significant side effects
(4). A variety of other agents have been used, including
tacrolimus, hyperbaric oxygen, mycophenolate mofetil,
dapsone and plasmapheresis. There have been no
prospective randomised controlled trials on any treatment.
For extreme intractable cases of PG, surgical intervention
may be required (5).
Infliximab, a monoclonal antibody that blocks and
neutralizes TNF-α. has demonstrated rapid improvement of
moderate to severe CD (6) and healing of fistulae in
randomised controlled trials (7). It induces endoscopic,
clinical as well as histological improvement and has been
approved by the FDA for the management of moderate to
severe CD and fistulizing CD. Improvement of CD’s
associated skin lesions and spondylo-arthropathy have also
been suggested. There have been several case reports and
retrospective studies that suggest that Infliximab may induce
healing of PG lesions in patients with CD (4,8-11). There are
also reports of successful treatment of ulcerative colitis as-
Kouklakis et al
sociated PG with Infliximab (12,13). In these reports both
skin lesions and bowel disease responded well to Infliximab
administration. Improvement of skin lesions occurred soon
after the administration of Infliximab, and complete or nearly
complete healing was achieved in less than 3 months after
the first infusion (14). Whether the positive effect of
Infliximab on PG is a result of effective treatment of the
intestinal inflammation or of the skin disease is not clear.
The outcome of Infliximab treatment in 8 patients with PG
associated with IBD was reported by Ljung et al (3). Three
of the patients responded with complete healing of PG,
defined as skin covering completely the lesion. Three
partially responded to Infliximab treatment, which was
defined as at least 50% reduction of the diameter of the
lesion and two had transitory improvement to Infliximab.
Adverse effects as skin rash, pneumonia and diarrhoea were
seen in three patients. The authors concluded that the
majority of patients with PG benefit from Infliximab treatment
with an acceptable occurrence of adverse reactions. In order
to achieve full remission, however, repeated treatment is
needed (3).
In a retrospective study, 13 patients with IBD and
medically refractory PG were treated with Infliximab. In three
of these patients PG lesions responded to the first Infliximab
infusion and did not require additional treatment, but most
of the patients required repeated infusions and were
ultimately maintained on Infliximab (4). Tan et al reported
two patients with PG and fistulizing CD and impressive
improvement after the first infusion of Infliximab. PG did
recur in both patients but responded to additional therapy
with Infliximab (10) . Mimouni et al described their experience
in three patients with IBD - associated peristomal PG. Two
of them had complete healing of the lesion and one partial
response to the drug (15). A 41-year old woman with known
CD had a severe and rapidly extensive corticosteroid
resistant PG on the leg. Infliximab 5mg/kg was given at weeks
0, 5 and 9. A complete healing was achieved at week 11 (16).
Infliximab should be considered for treating PG and other
extraintestinal dermatological manifestations in CD even in
children (17).
The durability of the response to Infliximab remains to
be established, and it is uncertain whether the best method
of treatment with infliximab is on demand or regularly.
The efficacy of Infliximab in many inflammatory diseases
has already been reported, but its use in PG has only been
seen in a few cases. Our case report suggests that Infliximab
is effective and safe therapy for refractory CD-associated
PG and should be included in the armamentarium of
medicines used to treat this skin lesion.
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