Buruli ulcer is a chronic and infectious skin disease, caused by Mycobacterium ulcerans. It leads to large skin ulceration and sometimes bone infection which is responsible for deformities. Here, we report a case of multifocal form of Buruli ulcer associated with secondary infection in a 46-year-old human immunodeficiency virus (HIV) positive woman. The antimycobacterial drugs combined to surgery allowed curing this multifocal case and rose up two relevant issues: the susceptibility of immune reconstitution inflammatory syndrome (IRIS) occurrence and Mycobacterium dissemination. The deep immune depression, the underline biological, and clinical disorders of the patient might contribute to IRIS occurrence and Buruli ulcer dissemination. Future investigations have to be conducted on the mechanism of IRIS on set and on Mycobacterium ulcerans dissemination after ARV drugs initiation and the patient related underline clinical or biological disorders

Ecra J Elidjé

Gbery P Ildevert

Kanga Jean-Marie

Kassi Komenan

Kouame Kanga

Kouassi A Kouamé

Kouassi I Yao

Kourouma S Hamdam

Sangaré Abdoulaye

Yoboué P Yao

CiteSeerX

Hindawi Publishing Corporation
Case Reports in Medicine
Volume 2013, Article ID 348628, 4 pages
http://dx.doi.org/10.1155/2013/348628
Case Report
Multifocal Buruli Ulcer Associated with Secondary Infection in
HIV Positive Patient
Kassi Komenan, Ecra J. Elidjé, Gbery P. Ildevert, Kouassi I. Yao,
Kouame Kanga, Kouassi A. Kouamé, Sangaré Abdoulaye, Kourouma S. Hamdam,
Yoboué P. Yao, and Kanga Jean-Marie
Department of Dermatology and Infectiology, School of Medicine, Felix Houphouét Boigny University of Abidjan,
BP 01 V166 Abidjan 01, Cote d’Ivoire
Correspondence should be addressed to Kassi Komenan; siskakomlo@yahoo.fr
Received 20 June 2013; Revised 6 December 2013; Accepted 12 December 2013
Academic Editor: T. Ottenhoff
Copyright © 2013 Kassi Komenan et al.This is an open access article distributed under the Creative Commons Attribution License,
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Buruli ulcer is a chronic and infectious skin disease, caused by Mycobacterium ulcerans. It leads to large skin ulceration and
sometimes bone infection which is responsible for deformities. Here, we report a case of multifocal form of Buruli ulcer associated
with secondary infection in a 46-year-old human immunodeficiency virus (HIV) positive woman. The antimycobacterial drugs
combined to surgery allowed curing thismultifocal case and rose up two relevant issues: the susceptibility of immune reconstitution
inflammatory syndrome (IRIS) occurrence and Mycobacterium dissemination. The deep immune depression, the underline
biological, and clinical disorders of the patient might contribute to IRIS occurrence and Buruli ulcer dissemination. Future
investigations have to be conducted on the mechanism of IRIS on set and on Mycobacterium ulcerans dissemination after ARV
drugs initiation and the patient related underline clinical or biological disorders.
1. Introduction
Buruli ulcer is mycobacterial disease, caused by Mycobac-
terium ulcerans. It is an emerging and neglected tropical
disease marked by devastating skin ulceration, and some-
times by bone lesion. Buruli ulcer represents a public health
problem in Cote d’Ivoire, where it remains endemic. Until
recently, surgery was the only treatment for this disease [1].
Since 2004, significant progress has been made and
Buruli ulcer is treated by rifampicin and streptomycin [2].
Multifocal forms of BU are rarely described in the literature
and they are sometimes associated with secondary infection
and human immunodeficiency virus (HIV) coinfection [3].
When associated with HIV coinfection, the use of antire-
troviral treatment (ART) has led to substantial decrease in
HIV-related morbidity andmortality, through preserving the
host’s immune system and reducing opportunistic infections.
However, complications associated with ART initiation,
including immune reconstitution inflammatory syndrome
(IRIS), are also increasingly described [4, 5]. Sometime, this
condition worsens ART initiation, mainly in developing
country such as Africa where ART is now available [6].
The disseminated process of Mycobacterium is not fully
understood, even if it was reported that it may be caused by
IRIS [7].
Here, we report a case in adult woman, who was hospi-
talized in the Department of Dermatology at the Teaching
Hospital of Treichville, for a multifocal form of BU associated
with secondary infection and HIV coinfection.
2. Case Report
It was a 46-year-old female patient, living in an endemic area
of BU (western part of Côte d’Ivoire) who was hospitalized
for several ulcerations on the two legs.
According to her, the disease started by nodules on the
left leg, associated with pain, hot edema, and local redness.
Two weeks later, the lesions evolved into a large ulceration.
As for this ulceration, she used some traditional medicines
before going to the community base medical center where an
2 Case Reports in Medicine
(a) (b)
(c)
Figure 1: (a) A large ulceration of the left leg associated with pain, redness, and hot edema and several small ulcerations with identical
features to the large one. (b) and (c) Several painless ulcerated nodules appeared on the body (head and bottom) after antiretroviral treatment
initiation.
antibiotic (none precised) was given to her and the wound
was dressed, without success.
Later, she observed new ulcerations on the right leg, and,
on the left one, the lesions extended and become painful with
fever. Then, the patient decided to go to the Dermatology
Department for better management.
The clinical examination was as follows.
(i) The general state of our patient was distorted with
a blood pressure of 130/80mmHg, a pulse of 88
beat/mn, and a temperature of 38.7∘C, associatedwith
minor cutaneous dehydration. Her weight was 63
kilograms.
(ii) Local examination showed the following.
(a) On the left lower limb, there is a large ulceration
(10 cm of diameter) that extends to the left
internal malleolus. The ulceration depth was
dirty, suppurative, yellow, and necrotic. Black
necrotic escharwith irregular border in different
areas of the ulcerations was associated with
pigmented surrounding skin. This ulceration
was associated with pain redness and hot edema
extended to the foot. Several small ulcerations
with identical features to the large one were
observed (Figure 1(a)).
(b) On the right leg, we noted a large ulceration
(12 cm of diameter) with identical features to the
left one.
(c) No lymph node and lymphangitis were found.
The peripheral pulse and sensibility of the two
lower limbs were normal.
We suspected secondary wound infection (bacterial)
based on the following features: a general distorted state, an
ulcerated, suppurative, and necrotic woundwith edema, local
redness, heat, pain, and fever.
We performed blood check examinations to confirm
the diagnosis, which showed a leukocyte count of 11000
cells/mm3, an anemia with 6.3 g/dL, a biological inflam-
matory syndrome, and hypoprotidemia. Kidney and liver
biological examination and blood sugar level were normal.
The X-ray of the lower limbs did not find any bone lesion.
Patient was taken to surgical emergency room to perform
surgery.
In a local level, a surgical excision and debridement of
necrotic tissues were performed on the two legs. Sample and
pus were taken from the necrotic tissues for microbiological
Case Reports in Medicine 3
examination including polymerase chain reaction (PCR).The
wound was dressed by antiseptic.
In the systemic level, the patient was put under clavulanic
acid + amoxicillin, 2 grams (g) per day, added to Paracetamol
of 1 g three times per day for 2 days, blood transfusion of 450
milliliters (mL) one time, and intravenous rehydration of 2
liters per day during 2 days. Ferrous was given on the third
day: 20 milligrams (mg) orally per day.
After 48 hours, the bacteriological examination of the
pus taken from the wound showed some streptococcus, the
polymerase chain reaction (PCR) examination of the biopsy
stain showedMycobacterium ulcerans, and histopathological
slides showed inflammatory cell with acid fast bacilli.
In addition, the HIV test was performed after counseling
and the patient consent was positive for HIV-1 with CD
4
cells
count of 51 cells/mm3.
We concluded to multifocal Buruli ulcer form associated
with secondary wound infection to streptococcus in HIV-1
positive patient.
The patient was treated by streptomycin (80mg intramus-
cular, one daily injection) combined to rifampicin (600mg
orally, once per day).
For the HIV-1 infection, the patient received ART by
combination of Stavudine (40mg) + Lamivudine (150mg) +
Nevirapine (200mg) twice a day during 2 weeks. For its
good tolerance and after liver and blood kidney test, this
combination was pursued.
One month later, several painless ulcerated nodules
appeared on the body (Figures 1(b) and 1(c)).
The PCR and histological examinations confirmedMyco-
bacterium ulcerans infection.
TheCD
4
cell count that moment was stable, 51 cells/mm3.
We hypothesized that it was either an immune reconstitu-
tion inflammatory syndrome due toMycobacterium ulcerans
or an inefficient ARV.
We decided to change the ARV combination; we used
Truvada (Emtricitabine 200mg + Tenofovir 245mg) once
a day combined to Kaletra (Lopinavir 200mg + Ritonavir
50mg) twice a day orally. All the ulcerated nodules were
excised and the antimycobacterial treatment was pursued
over the 8 weeks as recommended by WHO.
Two months later (from the beginning of the ART), half
of the lesions were cured; the CD
4
cell count gain was not
significant (53 cells/mm3). Unfortunately, we were not able
to perform viral load (which allow for real evaluation of the
ARV efficacy), and the hemoglobin was 9.8 g/dL; the patient
general state was good with neither fever nor cutaneous
dehydration.
At 3 months (from the beginning of the ART), CD4
cell count increased to 82 cells/mm3. Blood check found
hemoglobin to be 10.9 g/dL, and liver and kidney functions
were normal. We observed a total cicatrization of Buruli
ulcer lesions (Figure 2) and stopped the antimycobacterial
treatment.
At 6-month follow-up time, CD
4
cell count was 120
cells/mm3 and biological ART followup did not found any
abnormality.
Figure 2: Healed multifocal form of Buruli ulcer (left lower limb) at
3 months of followup.
3. Discussion
The two relevant aspects of this case report are, firstly, the
mechanism ofMycobacterium ulcerans dissemination in this
multifocal form of BU and, secondly, the difficulty to conduct
concomitantly BU treatment and ART.
The use of ART has considerably reduced HIV related
mortality, in terms of both opportunistic disease reduction
and preservation of patient immune system [6].
However, quantitative and qualitative recoveries of
pathogen-specific cellular and humoral responses have been
noted to multiple opportunistic pathogens including Myco-
bacterium (tuberculosis, leprea, avium, etc.) [8].
This paradoxical reaction or Immune reconstitution
inflammatory syndrome (IRIS) is recognized as a potential
complication that has been previously observed in HIV-
positive patient associatedwithMycobacterium infection.The
frequency of its occurrence is 10 to 25% of patient is that
received ART [8]. In Africa, this phenomenon became more
and more observed, due to ARV availability.
The interval between ART initiation and IRIS occurrence
is highly variable, fromone to several weeks. But, themajority
of IRIS occurs in patient with low mean CD
4
cell counts
(under 50 cells/mm3). Its onset is marked by paradoxal wors-
ening of clinical or laboratory parameters despite favorable
development of the surrogate markers [6]. The reaction may
arise in 2 different settings, depending on whether ART
was started in a patient treated for ongoing opportunistic
infections or in a clinically stable patient [8, 9].
Few cases of disseminated BU forms associated to HIV
coinfection were published [3, 10].
In our case, we started BU treatment two weeks before
initiating ART, and the paradoxal reaction or IRIS appeared
one month later, associated with fever and swelling.
The CD
4
cell count at the time of ART initiation was low
(51 cells/mm3) and the patient general state was distorted
associated to biological disorders.
This alliterated condition of the patient might favor the
onset of the paradoxal immune reaction. It may explain
the emergence of disseminated nodules of BU after ART
initiation.
4 Case Reports in Medicine
At one month of ART, The none significant CD
4
cells
count (53 cells/mm3) and the several BU and ulcerated nod-
ules allowed hypothesizing ART failing with Mycobacterium
dissemination favored by IRIS onset.Unfortunately, viral load
was not available in our setting, but we did not discard these
hypotheses.
So, we retained ART failing under Stavudine (40mg) +
Lamivudine (150mg) +Nevirapine (200mg) even if we could
not perform viral load in our setting. Therefore, the patient
was treated by another first line ARV combination using Tru-
vada (Emtricitabine 200mg + Tenofovir 245mg) associated
withKaletra (Lopinavir 200mg+Ritonavir 50mg) and added
4 weeks of antimycobacterial drugs treatment because of
disseminated lesions (12 weeks duration of treatment). Under
this treatment, the CD4 cell counts increased progressively at
2 months, at 3 months, and at 6 months (53 cells/mm3, 83
cells/mm3, and 120 cells/mm3).
In addition, all Buruli ulcer lesions were cured; the
patient general statewas significantly improved, including the
anemia, the dehydration, and the hypoprotidemia.
So, the underline conditions of the patient might con-
tribute to the onset of IRIS and the Mycobacterium dissem-
ination in this HIV-1 coinfection case. The distorted general
state of the patient added to the traditional medicine applied
on the wound contributed to the secondary wound infection
occurrence.
Moreover, ARV combination used in this case (Stavudine
(40mg) + Lamivudine (150mg) + Nevirapine (200mg)) did
not work because of Rifampicin usage. This drug decreases
nevirapine Cmax and Cmin. That must have explained why
this ARV combination failed in our case [11].
4. Conclusion
This case report highlights the difficulty to treat multifocal
form or Buruli ulcer associated with secondary wound
infection and HIV coinfection. This difficulty is related to
possible occurring of immune reconstitution inflammatory
syndrome and Mycobacterium ulceran dissemination which
needs to be well understood. Therefore, future studies need
to be conducted both on the mechanism of IRIS onset and on
Mycobacterium ulcerans dissemination in order to improve
the management of HIV infected patients.
References
[1] A. Chauty, M.-F. Ardant, L. Marsollier et al., “Oral treatment for
Mycobacterium ulcerans infection: results from a pilot study in
Benin,”Clinical InfectiousDiseases, vol. 52, no. 1, pp. 94–96, 2011.
[2] W. A. Nienhuis, Y. Stienstra, W. A. Thompson et al., “Antimi-
crobial treatment for early, limited Mycobacterium ulcerans
infection: a randomised controlled trial,” The Lancet, vol. 375,
no. 9715, pp. 664–672, 2010.
[3] A. Toll, F. Gallardo, M. Ferran et al., “Aggressive multifocal
Buruli ulcer with associated osteomyelitis in an HIV-positive
patient,” Clinical and Experimental Dermatology, vol. 30, no. 6,
pp. 649–651, 2005.
[4] D. P. O’Brien, M. E. Robson, P. P. Callan, and A. H. McDonald,
““Paradoxical” immune-mediated reactions to Mycobacterium
ulcerans during antibiotic treatment: a result of treatment
success, not failure,” Medical Journal of Australia, vol. 191, no.
10, pp. 564–566, 2009.
[5] A. Singal, S. Mehta, and D. Pandhi, “Immune reconstitu-
tion inflammatory syndrome in an HIV seropositive leprosy
patient,” Leprosy Review, vol. 77, no. 1, pp. 76–80, 2006.
[6] N. F. Crum-Cianflone, “Immune reconstitution inflammatory
syndromes: what’s new?” AIDS Reader, vol. 16, no. 4, pp. 199–
217, 2006.
[7] G. E. Sopoh, A. D. Dossou, L. V. Brun et al., “Case report: severe
multifocal form of buruli ulcer after streptomycin and rifampin
treatment: comments on possible dissemination mechanisms,”
American Journal of Tropical Medicine and Hygiene, vol. 83, no.
2, pp. 307–313, 2010.
[8] H.H.Hirsch,G.Kaufmann, P. Sendi, andM.Battegay, “Immune
reconstitution in HIV-infected patients,” Clinical Infectious
Diseases, vol. 38, no. 8, pp. 1159–1166, 2004.
[9] S. F. Stone, P. Price, M.-L. Tay-Kearney, and M. A. French,
“Cytomegalovirus (CMV) retinitis immune restoration disease
occurs during highly active antiretroviral therapy-induced
restoration of CMV-specific immune responses within a pre-
dominant Th2 cytokine environment,” Journal of Infectious
Diseases, vol. 185, no. 12, pp. 1813–1817, 2002.
[10] R. C. Johnson, D. Ifebe, A. Hans-Moevi et al., “Disseminated
Mycobacterium ulcerans disease in an HIV-positive patient: a
case study [9],” AIDS, vol. 16, no. 12, pp. 1704–1705, 2002.
[11] WHO, “WHO 7.4. monitoring and substitute for ARV drug
toxicities,” Consolidate ARVGuidelines, 2013, http://www.who.
int/hiv/pub/guidelines/arv2013/art/drugstoxicities/en/index5
.html.
Submit your manuscripts at
http://www.hindawi.com
Stem Cells
International
Hindawi Publishing Corporation
http://www.hindawi.com Volume 2014
Hindawi Publishing Corporation
http://www.hindawi.com Volume 2014
MEDIATORS
INFLAMMATION
of
Hindawi Publishing Corporation
http://www.hindawi.com Volume 2014
Behavioural 
Neurology
Endocrinology
International Journal of
Hindawi Publishing Corporation
http://www.hindawi.com Volume 2014
Hindawi Publishing Corporation
http://www.hindawi.com Volume 2014
Disease Markers
Hindawi Publishing Corporation
http://www.hindawi.com Volume 2014
BioMed 
Research International
Oncology
Journal of
Hindawi Publishing Corporation
http://www.hindawi.com Volume 2014
Hindawi Publishing Corporation
http://www.hindawi.com Volume 2014
Oxidative Medicine and 
Cellular Longevity
Hindawi Publishing Corporation
http://www.hindawi.com Volume 2014
PPAR Research
The Scientific 
World Journal
Hindawi Publishing Corporation 
http://www.hindawi.com Volume 2014
Immunology Research
Hindawi Publishing Corporation
http://www.hindawi.com Volume 2014
Journal of
Obesity
Journal of
Hindawi Publishing Corporation
http://www.hindawi.com Volume 2014
Hindawi Publishing Corporation
http://www.hindawi.com Volume 2014
 Computational and  
Mathematical Methods 
in Medicine
Ophthalmology
Journal of
Hindawi Publishing Corporation
http://www.hindawi.com Volume 2014
Diabetes Research
Journal of
Hindawi Publishing Corporation
http://www.hindawi.com Volume 2014
Hindawi Publishing Corporation
http://www.hindawi.com Volume 2014
Research and Treatment
AIDS
Hindawi Publishing Corporation
http://www.hindawi.com Volume 2014
Gastroenterology 
Research and Practice
Hindawi Publishing Corporation
http://www.hindawi.com Volume 2014
Parkinson’s 
Disease
Evidence-Based 
Complementary and 
Alternative Medicine
Volume 2014
Hindawi Publishing Corporation
http://www.hindawi.com


Case Report Multifocal Buruli Ulcer Associated with Secondary Infection in HIV Positive Patient

http://citeseerx.ist.psu.edu/viewdoc/download;jsessionid=A3BCB231EC02D4D7F159AA8A9C8FF883?doi=10.1.1.1075.8001&rep=rep1&type=pdf

Case Report Multifocal Buruli Ulcer Associated with Secondary Infection in HIV Positive Patient

Abstract

Similar works

Full text

Available Versions

CiteSeerX