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QJM Advance Access published March 18, 2015
LEISHMANIASIS, LUPUS NEPHRITIS AND
IMMUNOSUPPRESSIVE THERAPY
Case Report
Authors: José Antonio Vargas-Hitos MD, PhD (1); Ricardo Roa-Chamorro MD (1);
José Mario Sabio MD, PhD (1); Rosario Javier-Martínez MD (2); Aurelio MartínCastro MD, PhD (3); Juan Jiménez-Alonso MD, PhD (1).
(1): Systemic Autoimmune Diseases Unit, Internal Medicine Department. ¨ Virgen de
las Nieves ¨ University Hospital, Granada. Spain.
(2): Infectious Diseases Department. ¨ Virgen de las Nieves ¨ University Hospital,
(3): Histopathology Department. ¨ Virgen de las Nieves ¨ University Hospital, Granada.
Spain.
Correspondence to:
Dr. José Antonio Vargas Hitos, Internal Medicine Department, 9th floor, ¨ Virgen de las
Nieves University Hospital ¨, Avda. Fuerzas Armadas Nº 2, 18012 Granada, Spain.
Telephone & Fax: +34-958-020158.
E-mail: [email protected]
Running head: Mucocutaneous leishmaniasis in lupus.
Key indexing terms: Mucocutaneous leishmaniasis, systemic lupus erythematosus,
mycophenolate mofetil.
Conflict of interest: None declared.
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Granada. Spain.
Leishmaniasis is an infectious disease in which immunosupression is a well-known risk
factor for its development. We report the first case of a patient with systemic lupus
erythematosus (SLE) who was diagnosed of mucocutaneous leishmaniasis (ML) while
taking mycophenolate mofetil (MMF) for lupus nephritis.
A 51 year-old woman from the south of Spain with an eight-year history of SLE was
diagnosed with diffuse proliferative glomerulonephritis six years after her SLE
diagnosis, which was satisfactorily treated until complete remission was achieved with
MMF (1 g b.i.d) and decreasing doses of prednisone (from 30 mg to 10 mg q.d). The
patient complained of inflammation in the right nasal vestibule that started three years
after SLE diagnosis but especially enlarged 10 months after the diagnosis of lupus
nephritis was made. At the moment of consultation, the patient admitted nose-breathing
except for an ulcerated lesion in her right nostril with a surrounding area of
inflammation (Fig. 1a). Laboratory findings showed 3300 x 103/uL leukocytes, C
reactive protein of 4 mg/dL and normal lymphocyte populations. Serologies for
Leishmania and HIV were negative. A biopsy of the lesion was performed, observing
multiple small spheroid structures inside the macrophages that stained with Giemsa
consistent with Leishmania amastigotes (Fig. 1b). Moreover, cultures of the lesion and
PCR techniques identified Leishmania infantum, confirming the diagnosis of ML.
Treatment with amphotericin B was initiated (3 mg/kg during five days followed by five
weekly infusions at the same doses) and a progressive resolution of the lesion with no
signs of nephrotoxicity was observed.
Leishmaniasis is a vector-born infectious disease caused by obligate intracellular
parasites of the genus Leishmania that infect macrophages. Depending on the species of
Leishmania and the host’s immune status, three types of leishmaniasis can be
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difficulties but denied any systemic symptom. Physical examination was unremarkable
differentiated: visceral, cutaneous and mucocutaneous 1. Immunosuppression may
encourage either reactivation from a latent leishmaniasis infection (as in our case) or
failure to control a new infection 2. Nowadays, non-HIV related immunosuppressive
conditions are becoming increasingly prevalent given the common use of powerful
immunosuppressive therapies. As a result, visceral leishmaniasis (VL) has been
previously reported in multiple rheumatic diseases, such as SLE, rheumatoid arthritis
(RA) and systemic vasculitis 2. ML refers to ulcerative lesions that normally involve the
skin and mucosa of the nose, septum and mouth. Diverse case reports have described
the relationship between the use of different types of immunosuppressant agents, mainly
anti-TNF-α drugs, and ML development in patients with rheumatic diseases, such as
RA, psoriatic arthritis (PA) and ankylosing spondylitis (AS) 2,3.
opportunistic infections, such as cytomegalovirus and BK virus, infection by
Leishmania is uncommon and normally restricted to transplantation medicine 4. In
contrast, this association has not been described so far in patients with rheumatic
diseases. With regard to SLE patients in particular, only three cases of visceral
leishmaniasis (but not ML) have been reported up until now and all of them were
associated with the use of corticosteroids as the only immunosuppressant risk factor 5-7.
Therefore, our case describes the first ML related to MMF treatment in a patient with
SLE, although we think the immunosuppressive effect of corticosteroids and SLE itself
also played a role in the development of ML.
In conclusion, despite ML is a rare complication in rheumatic patients treated with
MMF, nowadays is a worldwide disease with increasing incidence which should be
considered among the opportunistic infections that may develop during MMF therapy.
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Even though the use of MMF has been associated with an increased risk of
Learning Point
Mucocutaneous leishmaniasis is an increasingly common opportunistic infection that
should be considered during treatment with mycophenolate mofetil, especially when
other immunosuppressant drugs (such as corticosteroids) or diseases (such as SLE) are
present.
Legends
Figure 1a: Ulcerated lesion in the right nostril with surrounding inflammation.
Figure 1b: Skin inflammation with dense lymphohistiocytic infiltrate and abundant
small spheroidal structures inside macrophages, which are stained with Giemsa
(magnification 200x).
1. McGwire BS, Satoskar AR. Leishmaniasis: clinical syndromes and treatment. QJM
2014;107:7-14.
2. van Griensven J, Carrillo E, López-Vélez R, Lynen L, Moreno J. Leishmaniasis in
immunosuppressed individuals. Clin Microbiol Infect 2014;20:286-99.
3. Guedes-Barbosa LS, Pereira da Costa I, Fernandes V, Henrique da Mota LM, de
Menezes I, Aaron Scheinberg M. Leishmaniasis during anti-tumor necrosis factor
therapy: report of 4 cases and review of the literature (additional 28 cases). Semin
Arthritis Rheum 2013;43:152-7.
4. Ritter ML, Pirofski L. Mycophenolate mofetil: effects on cellular immune subsets,
infectious complications, and antimicrobial activity. Transpl Infect Dis
2009;11:290-7.
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References
5. Braun J, Sieper J, Schulte KL, Thiel E, Janitschke K. Visceral leishmaniasis
mimicking a flare of systemic lupus erythematosus. Clin Rheumatol 1991;10:445-8.
6. Ossandon A, Bompane D, Alessandri C, Marocchi E, Conti F, Valesini G.
Leishmania in SLE mimicking an exacerbation. Clin Exp Rheumatol 2006;24:18690.
7. Pérez Silvestre J, Campos Fernández C, Calvo Catalá J, González Cruz MI, Baixauli
Rubio A, Pastor Cubillo D. Unfrequently opportunistic infection
in lupus erythematosus with inmunosuppresive treatment. An Med Interna
2007;24:177-8.
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Acronyms
SLE: Systemic lupus erythematosus.
ML: Mucocutaneous leishmaniasis.
MMF: Mycophenolate mofetil.
VL: visceral leishmaniasis.
RA: Rheumatoid arthritis.
PA: Psoriatic arthritis.
AS: Ankylosing spondylitis.
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Ulcerated lesion in the right nostril with surrounding inflammation.
254x190mm (72 x 72 DPI)
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Skin inflammation with dense lymphohistiocytic infiltrate and abundant small spheroidal structures inside
macrophages, which are stained with Giemsa (magnification 200x).
175x131mm (300 x 300 DPI)