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I n t e r n a t i o n a l J o u r n a l o f M y c o b a c t e r i o l o g y x x x ( 2 0 1 3 ) x x x – x x x
.sc ienced i rec t .com
IJMYCO 84 No. of Pages 3, Model 7
16 August 2013
Avai lab le a t www
ScienceDirect
journal homepage: www.elsevier .com/ locate / IJMYCO
Case Report
Cutaneous leukocytoclastic vasculitis revealing multifocaltuberculosis
Meziane Mariame a,*, Amraoui Nisrine a, Taoufik Harmouch b, Mernissi Fatima Zahra a
a Dermatological Department, Hassan II University Hospital, Fes, Moroccob Laboratory of Pathology, Hassan II University Hospital, Fes, Morocco
A R T I C L E I N F O
Article history:
Received 21 July 2013
Accepted 29 July 2013
Available online xxxx
2212-5531/$ - see front matter � 2013 Publishttp://dx.doi.org/10.1016/j.ijmyco.2013.07.004
* Corresponding author. Tel.: +212 6637124E-mail address: mariame_meziane@yaho
Please cite this article in press as: M Mariame e(2013), http://dx.doi.org/10.1016/j.ijmyco.2013.
A B S T R A C T
Cutaneous leukocytoclastic vasculitis (CLV) is an inflammatory vascular disorder rarely
reported to be associated with tuberculosis. The following report describes the case of a
young man with multifocal tuberculosis revealed by CLV. Diagnosis was confirmed by the
presence of tuberculoid granuloma with caseous necrosis on pleural and perianal biopsy,
and a rapid improvement in anti-tuberculous quadritherapy.
Although rarely seen, Mycobacterium tuberculosis should be considered as a potential
cause of CLV.
� 2013 Published by Elsevier Ltd. on behalf of Asian-African Society for Mycobacteriology.
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Introduction
Cutaneous leukocytoclastic vasculitis (CLV) is an inflamma-
tory vascular disorder due to deposition of immune com-
plexes in dermal vessels. It can have several causes,
including drugs, malignancy, collagen vascular disease, and
infection [1]. Among the infectious agents, bacteria are well
recognized as causes of CLV, but Mycobacterium tuberculosis
is rarely reported to be associated with CLV [2–4].
The following reports the case of a young man with multi-
focal tuberculosis whose initial presentation was that of a
lower limb leukocytoclastic vasculitis. This case seems to be
the first case reporting this association and discussing the
possible mechanisms.
Observation
A 19-year-old man with a history of perianal swelling for
1 month was admitted to the dermatological department
with a 1 week history of erythematous lesions of the lower
limbs, fever, abdominal pain, and arthralgia of the knees,
hed by Elsevier Ltd. on b
31.o.fr (M. Mariame).
t al. Cutaneous leukocytocl07.004
ankles and wrists with weight loss. He had no other personal
or familial history and had not taken any medications re-
cently. Upon physical examination, the finding was the pres-
ence on both legs of several palpable purpuric lesions that
coalesced, resulting in vesicles (Fig. 1). Clinical examination
also showed a 2 cm anal ulceration and a pleural left effusion.
The blood workup revealed that the blood count, serum
creatinine, aspartate aminotransferase and alanine amino-
transferase were normal. The erythrocyte sedimentation rate
was 32 mm in the first hour, and the level of C-reactive pro-
tein was also elevated at 152 mg/l.
Serological markers for HIV, cytomegalovirus, Epstein-Barr
virus, hepatitis B and C, and syphilis were all negative. Rheu-
matoid factor, antinuclear antibody, anti-dsDNA antibody,
and anti-neutrophil cytoplasmic antibody (ANCA) were also
negative. Complement level was normal.
A chest X-ray showed a cavern in the right superior lobe
and a left pleurisy (Fig. 2). A sputum smear microscopy
(Ziehl–Neelsen staining) was negative in three consecutive
samples and skin testing with purified protein derivative
(PPD) was positive (induration of 14 mm).
ehalf of Asian-African Society for Mycobacteriology.
astic vasculitis revealing multifocal tuberculosis. Int. J. Mycobacteriol.
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Fig. 1 – Purpuric lesions of the dorsum of the foot.
Fig. 2 – A chest X-ray, showing a cavern in the right superior
lobe and a left pleurisy.
2 I n t e r n a t i o n a l J o u r n a l o f M y c o b a c t e r i o l o g y x x x ( 2 0 1 3 ) x x x – x x x
IJMYCO 84 No. of Pages 3, Model 7
16 August 2013
A skin biopsy of the purpuric lesions was carried out. The
pathological skin analysis revealed leukocytoclastic vasculitis
(neutrophilic vasculitis of the small superficial vessels) and
immunofluorescence did not show the deposit of immuno-
globulin or complement. A pleural and perianal biopsy
showed tuberculoid granuloma with caseous necrosis. Poly-
merase chain reaction (PCR) determination of Mycobacterium
tuberculosis lesions was not done. A rectoscopy and colonos-
copy were normal. There were no signs of vasculitis present
in the internal organs.
The patient was diagnosed with CLV associated with mul-
tifocal tuberculosis (pleural, pulmonary and anal). He was
put under confinement to one’s bed and anti-tuberculosis
treatment was initiated with isoniazid, rifampin, pyrazina-
mide and ethambutol for 2 months followed by 7 months
of rifampicin and isoniazid, with a good response and toler-
ance. The skin lesions showed gradual remission until
complete resolution after 2 weeks of treatment, the anal le-
sion healed after 1 months and pleurisy after 4 weeks.
During the 6-month course of treatment, there was no recur-
rence of purpura on the skin. A 2-year follow-up was
recommended.
Discussion
CLV secondary to Mycobacterium tuberculosis is uncommon
with less than 20 cases reported currently [2–8].
Please cite this article in press as: M Mariame et al. Cutaneous leukocytocl(2013), http://dx.doi.org/10.1016/j.ijmyco.2013.07.004
Three main forms of the combination of tuberculosis and
vasculitis were described in literature: pulmonary tuberculo-
sis/Henoch–Schonlein purpura; pulmonary tuberculosis/vas-
culitis secondary to rifampicin and pulmonary tuberculosis/
cutaneous leukocytoclastic vasculitis [8]. In this third cate-
gory, as in this case, CLV was described in 12 patients, aged
between 13 and 61 years old, with a slight male predomi-
nance [4–6,9].
In those 12 cases of CLV reported, vasculitis was associated
with pulmonary tuberculosis in 7 cases [4–6,9] and with tuber-
culous lymphadenitis in 4 cases [2,4], while the site of Myco-
bacterium tuberculosis infection was not found in 1 patient
[3]. It is believed that this observation is the first to date
describing the association between multifocal tuberculosis
and CLV.
Clinically, CLV appears as palpable purpuric lesions on
both lower legs which can progressively spread to both thighs
or be accompanied by systemic symptoms as in this patient.
Purpura can be the first symptom of the disease or it can be
part of the overall clinical profile [6].
Histologically, the lesion is an angiocentric inflammatory
process associated with leukocytoclasia (neutrophil fragmen-
tation) and fibrinoid necrosis without the presence of Myco-
bacterium tuberculosis in the small vessel wall, which
differentiates it from cutaneous tuberculosis, in which micro-
organisms are seen in biopsy samples [6].
Even if cutaneous leukocytoclastic vasculitis is rare, it is
reported in the literature in young individuals with otherwise
normal immunity, with chronic and untreated tuberculosis [8]
as was the profile of this patient. The exact pathogenesis of
CLV due to Mycobacterium tuberculosis remains unknown,
astic vasculitis revealing multifocal tuberculosis. Int. J. Mycobacteriol.
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I n t e r n a t i o n a l J o u r n a l o f M y c o b a c t e r i o l o g y x x x ( 2 0 1 3 ) x x x – x x x 3
IJMYCO 84 No. of Pages 3, Model 7
16 August 2013
however, several mechanisms have been proposed: direct
invasion of vessel walls by tubercle bacilli; immunological
reaction involving the deposition of immune complexes;
intravascular release of mycobacteria followed by Arthus
reaction and delayed type hypersensitivity response; or Rif-
ampicin-dependent antibody and then immune complex for-
mation [8]. In this case, it is believed that an intravascular
release of mycobacteria from digestive, pulmonary tubercu-
lous pleural locations, which are highly vascularized, partici-
pated to the direct invasion of vessel walls by mycobacterium
tuberculosis.
Cutaneous leukocytoclastic vasculitis is treated by treating
the underlying disease; as in this case, a symptomatic treat-
ment of cutaneous lesions and anti-tuberculosis medication
are always sufficient with no recurrence after therapy [4]. In
hypersensitivity vasculitis caused by anti-tuberculosis ther-
apy (for example, rifampicin), discontinuation of the medica-
tion and its replacement improve skin lesions [6]. Severe skin
manifestations can be treated with a brief course of oral cor-
ticosteroids [1].
This report described a case of multifocal tuberculosis
associated with CLV confirmed by histology and therapy.
Although rarely seen, Mycobacterium tuberculosis should be
considered as a potential cause of CLV.
Financial support
None.
Conflict of interest
None declared.
Please cite this article in press as: M Mariame et al. Cutaneous leukocytocl(2013), http://dx.doi.org/10.1016/j.ijmyco.2013.07.004
R E F E R E N C E S
[1] J.C. Jennette, R.J. Falk, Small-vessel vasculitis, N. Engl. J. Med.337 (1997) 1512–1523.
[2] A.Y. Lee, J.H. Jang, L.K. Hee, Two cases of leukocytoclasticvasculitis with tuberculosis, Clin. Exp. Dermatol. 23 (1998) 225–226.
[3] G. Sais, A. Vidaller, A. Jucgla, J. Peyri, Tuberculouslymphadenitis presenting with cutaneous leukocytoclasticvasculitis, Clin. Exp. Dermatol. 21 (1996) 65–66.
[4] H.M. Kim, Y.B. Park, H.Y. Maeng, S.K. Lee, Cutaneousleukocytoclastic vasculitis with cervical tuberculouslymphadenitis: a case report and literature review, Rheumatol.Int. 26 (2006) 1154–1157.
[5] P.G. Stavropoulos, D.C. Boubouka, N.V. Anyfantakis, K.A.Panagiotopoulos, G.P. Kostakis, S. Georgala, et al, Cutaneoussmall vessel vasculitis and pulmonary tuberculosis: anunusual association, Int. J. Dermatol. 45 (2006)996–998.
[6] M. Carvalho, R.L. Dominoni, D. Senchechen, A.F. Fernandes, I.P.Burigo, E. Doubrawa, Cutaneous leukocytoclastic vasculitisaccompanied by pulmonary tuberculosis, J. Bras. Pneumol. 34(2008) 745–748.
[7] K. Chanprapaph, W. Roongpisuthipong, K. Thadanipon,Annular leukocytoclastic vasculitis associated with anti-tuberculosis medications: a case report, J. Med. Case Rep. 7(2013) 34.
[8] C.H.S. Chan, Y.W. Chong, A.J.M. Sun, G.B. Hoheisel, Cutaneousvasculitis associated with tuberculosis and its treatment,Tubercle (1990) 297–300.
[9] M.E. Guisado Espartero, A Dominguez Castellano, M.D.Fernandez Alba, Cutaneous leukocytoclastic associated topulmonary tuberculosis, Reumatol. Clin. 3 (2007)278–279.
astic vasculitis revealing multifocal tuberculosis. Int. J. Mycobacteriol.