Remission of Metastatic Crohn's Disease Achieved with Dapsone: A Case Report and Review of the Literature
Antonio Guglielmetti1, Matías Gompertz2,
Catalina Jahr3, Sergio González4, Tomás Silva3
1Chief of Dermatology Department,
University of Valparaíso, Chile
2Dermatology resident, Pontifical
Catholic University, Chile
3Medical student, University of
Valparaíso, Chile
4Chief of Pathology Department,
Pontifical Catholic University, Chile
*Corresponding
author: Antonio Guglielmetti. Chief of Dermatology Department,
University of Valparaíso, Chile Tel: +56-998260809; Email: antonioguglielmetti@yahoo.it
Received Date: 01 February, 2017; Accepted Date: 24 February, 2017; Published Date: 02 March, 2017
Citation: Guglielmetti A, Gompertz M, Jahr C, González S, Silva T
(2017) Remission of Metastatic Crohn's Disease Achieved with Dapsone: A Case
Report and Review of the Literature. Clin Exp Dermatol Ther 2017:
J116 DOI: 10.29011/2575-8268/100016
Metastatic Crohn’s disease (MCD) is a
rare manifestation of Crohn's disease (CD) defined by the presence of
infiltrating granulomatous skin lesions in areas anatomically separate from the
affected bowel sites. In adults, it is usually seen in patients already
diagnosed with CD, while in children it can be the first manifestations of CD.
There is no solid evidence to recommend treatment. We present a case of MCD
successfully treated with oral dapsone achieving complete remission after
failure of corticosteroids.
1. Introduction
Dapsone is an
antibiotic of the sulfone family with bacteriostatic, anti-inflammatory and
immunomodulatory effects. As an antibacterial, it inhibits bacterial synthesis
of dihydrofolic acid via competition with para-amino-benzoate for the active
site of dihydropteroate synthetase. The anti-inflammatory and immunomodulatory
effects are still not fully understood and it’s thought the to act through the
blockade of myeloperoxidase. It’s effective in inflammatory diseases that have
in common an infiltration of large numbers of polymorphonuclear leukocytes,
predominantly neutrophils [1,2].
There is no
solid evidence to recommend treatment in MCD. MCD usually has a chronic course
with exacerbations and remissions and treatment is often unsuccessful [3,4].
Corticosteroids and antibiotics (mainly metronidazole) are the most used
therapies described in the literature [3-5]. Biologic therapies have become an
important tool for managing a number of inflammatory dermatoses, and are often
used to sustain remissions of CD. Their use for the treatment of MCD has also
been recognized. Specifically, the TNF-alfa inhibitors adalimumab and
infliximab have been used successfully in cases of MCD refractory to
traditional therapies [6-8] never the less, its use in our country is limited
by the high cost. The use of dapsone has been mentioned in few cases of
cutaneous manifestations of CD, but not as treatment in MCD [1,2].
2. Case Report
An 82-year-old
woman diagnosed with Crohn’s disease 20 years ago with colostomy due to total
proctocolectomy, presented with a 2-year story of painful lesions on her groin,
genital region and gluteal cleft, with exacerbations and partial remissions. 10
years ago she had similar lesions in her infraabdominal fold with spontaneous
resolution (Figures 1-3).
On examination,
erythematous plaques with shiny surface, erosions and multiple ulcers with
little purulent exudate were seen in the mentioned areas. Routine laboratory
tests were normal. Skin biopsy showed perivascular and periadnexal noncaseating
granulomas, with numerous giant cells and dermis with perivascular lymphocytic
infiltration. The diagnosis of metastatic Crohn’s disease was made.
We first started
topical therapy with corticosteroids and antibiotics along with oral prednisone
(0.5 milligram per kilogram per day). There was no significant improvement, so
a change to dapsone was made, raising the dose up to 150 milligram per day with
fast and significant response, achieving almost full remission in three months
(Figure 5,6).
3. Discussion
MCD is
considered a rare disease, therefore it doesn’t exist enough evidence to
support any specific treatment, although multiple case-report therapies have
been informed as successful [3-5]. Even though spontaneous resolution of MCD
has been described, it is infrequent and unpredictable, usually behaving as a
chronic disease with multiple relapses. Medical treatment is frequently
unsuccessful [3,4].
It is essential
not just to treat MCD, but to manage with expertise CD, as this varies severity
of the presentation. A retrospective review of 700 cases of CD suggested that
skin lesions occur more frequently in patients with colon involvement compared
with those having ileal involvement alone [9] this finding was supported by a
subsequent large review [10].
It is important
to highlight that surgical resection of the affected bowel does not guarantee
resolution of CD nor the skin lesions [3,4,11]. Severity of EC is not
correlated with skin manifestations [3,12,13]. Most investigators have failed
to detect a connection between the activity of skin and GI lesions [14,15].
MCD is
considered an autoimmune chronic inflammatory disease, and the first choices of
treatment are immunosupressors. Corticosteroids are considered the first line
of treatment, either topical of high potency, or oral as prednisone 30 mg/day,
with progressive reduction. There are reports in literature that validate the
use of oral metronidazole in high doses 800-1500 mg/day for at least 4 months.
Other drugs such as metotrexate, azatioprine, ciclosporine and tacrolimus have
also been used. In refractory MCD, biological treatment has been used
(infliximab yadalimumab) [3,4,5,16].
There are no
randomized clinical studies nor case reports of dapsone efficacy in MCD. The
only information available is of its use in managing CD and skin lessions
secondary to CD and refractory to conventional treatment. Cutaneous
manifestations of CD not MCD respond well to treatment with dapsone, achieving
full recovery in most cases [17-20].
Given the similar
pathophysiologic and histology between EC and MCD, we thought dapsone to be a
valid therapeutic option in view of the results previously described.
Dapsone toxicity
may be categorized as either dose-dependent or idiosyncratic reaction. Most of
the side effects are dose related and uncommon at doses lower than 100 mg/day.
It’s relevant to mention that the most dangerous adverse effects of dapsone are
DRESS syndrome and hematologic alterations such as methemoglobinemia, aplastic
anemia, leukopenia, agranulocytosis, eosinophilia, macrocytic anemia and Heinz
bodie, which are
dose-dependent and more common and severe in patients with gluclose-6-phosphate
dehydrogenase deficiency. Patients generally tolerate 100 mg/day with very
little hemolysis, at doses of 200-300 mg/day all patients develop hemolysis
[1,2].
In summary, in
MCD refractory to first line treatment with corticosteroids and metronidazole,
dapsone should be considered as an alternative, taking into account the full
recovery observed in our patient and the evidence available in the literature.
Unfortunately, there is no solid evidence for it to be recommended, bearing in
mind the low frequency of this disease, which complicate investigation.
Figure 1: Lesions in the groin and genital area
Figure 2: Lesions in the genital area
Figure 3: Lesions in the gluteal cleft
Figure 4: Lesions in the genital region after treatment with dapsone
Figure 5: Lesions in the groin after treatment with dapsone
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