Reactivation of cutaneous and mucocutaneous tegumentary leishmaniasis in rheumatoid arthritis patients: an emerging problem?

Abstract

Rheumatoid arthritis (RA) is a chronic condition that is frequent in patients living in tropical areas exposed to leishmaniasis. RA therapy involves immunosuppressant drugs such as methotrexate (MTX), monoclonal antibodies (mAbs) and prednisone. We report an unusual presentation of cutaneous (CL) or mucocutaneous leishmaniasis (ML) in RA patients from an endemic area of leishmaniasis. A 51-year-old woman noted a cutaneous ulcer on her left ankle during MTX and prednisone RA therapy. Initially diagnosed as a venous stasis ulcer, the aspirate of the injury revealed the presence of Leishmania DNA. A 73-year-old woman presenting non-ulcerated, infiltrated and painful erythematous nodules inside her nostrils while receiving MTX, anti-TNF mAb, and prednisone for RA, had also the aspirate of injuries showing the presence of Leishmania DNA. Both patients healed after the therapy with liposomal amphotericin. The RA therapy has changed to low-dose prednisone, without further reactivation episodes. Both cases suggest that CL or ML can reactivate after administration of an immunosuppressant for RA treatment. Therefore, immunosuppressive treatments for RA should be carefully prescribed in patients from endemic areas or with a history of CL and ML.

The Binomial Parasite-Host Immunity in the Healing Process and in Reactivation of Human Tegumentary Leishmaniasis

“…There are numerous causes of immunosuppression in human patients, for example HIV infection, cancer, immunosuppressive treatments and transplantation. The association between immunosuppression and atypical cutaneous manifestations of leishmaniasis was systematically reviewed in a previous study ( Meireles et al, 2017 ) and described as case reports by several authors ( Gontijo et al, 2002 ; Tuon et al, 2007 , 2014 ; Mortazavi et al, 2014 ; Souza et al, 2017 ; among others). In a case of a kidney transplant patient infected with L. braziliensis , a concurrent cutaneous, visceral and ocular leishmaniasis was observed ( Gontijo et al, 2002 ).…”

“…The association of anti-TNF therapy and the increased risk for developing opportunistic infections has also been associated ( Neumayr et al, 2013 ; Calabrò et al, 2016 ). Regardless of the fact that most of the cases published showed a reactivation of visceral leishmaniasis, cases of association between rheumatoid arthritis (RA) and ATL were also described ( Souza et al, 2017 ). Despite the increasing amount of information available, most physicians still have problems to rapidly diagnose cutaneous leishmaniasis (CL) or mucosal leishmaniasis (ML) in patients submitted to immunosuppressive treatment since these patients very often show epidemiological evidence of previous leishmaniasis, however, they live in non-endemic regions of neglected tropical diseases at the time of diagnosis.…”

“…Once achieved, this equilibrium is maintained by the relation between T reg cells and effector lymphocytes ( Mendez et al, 2004 ). Trauma, elderly patients, comorbidities, co-infections and immunosuppression can destabilize this equilibrium leading to reactivation of the lesion ( Oliveira-Neto et al, 1998 ; Lages et al, 2008 ; Azeredo-Coutinho et al, 2016 ; Souza et al, 2017 ; Martínez et al, 2018 ).…”

Mucosal leishmaniasis mimicking T-cell lymphoma in a patient receiving monoclonal antibody against TNFα

“…The highlights of this article are the possibility of the reactivation of latent infections in patients receiving treatment with monoclonal antibodies for inflammatory and/or chronic autoimmune disease [ 3 ] and the need to consider these infections in the clinical and laboratorial differential diagnosis of tissue lesions in order to avoid misdiagnosis and wrong treatments.…”

“…Mucosal leishmaniasis should be part of the differential diagnosis of nasal lesions in patients on an immunosuppressive regimen, particularly those on anti-TNFα drugs [ 3 , 8 ]. Diagnosis can be challenging, and the T-cell–mediated response induced by the parasite can render immunohistochemical analysis difficult, leading to misdiagnosis with nasal lymphoma.…”