Home » Table of Content » Visceral leishmaniasis mimicking systemic lupus erythematosus

Visceral leishmaniasis mimicking systemic lupus erythematosus

Greyce Christine Lisboa Bueno, Amanda Terra de Sá Koerich, Luciana Bonnassis Burg, Sara Letícia Kretzer, Joanita Ângela Gonzaga Del Moral, Ivânio Alves Pereira

1Departamento de Clínica Médica, Hospital Universitário Polydoro Ernani de São Thiago, Universidade Federal de Santa Catarina, Florianópolis, SC, Brasil. 2Serviço de Reumatologia, Hospital Universitário Polydoro Ernani de São Thiago, Universidade Federal de Santa Catarina, Florianópolis, SC, Brasil. 3Departamento de microbiologia, Hospital Universitário Polydoro Ernani de São Thiago, Universidade Federal de Santa Catarina, Florianópolis, SC, Brasil. 4Serviço de Hematologia, Hospital Universitário Polydoro Ernani de São Thiago, Universidade Federal de Santa Catarina, Florianópolis, SC, Brasil.

DOI: 10.1590/0037-8682-0208-2018

ABSTRACT

Visceral leishmaniasis (VL), or kala-azar, a serious disease resulting from a systemic infection caused by a protozoan of the genus Leishmania, is potentially fatal to humans. According to data from Sistema de Informação de Agravos de Notificação (Brazil’s Information System for Notifiable Diseases) from 2015 to 2016, 6,489 new cases were recorded in Brazil in 22 of the 27 federative units. In addition to typical clinical findings, VL may be associated with autoimmune phenomena, including simulating systemic lupus erythematosus (SLE). We present the first case of autochthonous VL mimicking SLE in Santa Catarina in southern Brazil.

Keywords: Leishmaniasis; Kala-azar; Systemic lupus erythematosus

INTRODUCTION

Visceral leishmaniasis (VL), or kala-azar, a serious disease that is potentially fatal to humans, results from a systemic infection caused by a protozoan of the genus Leishmania, which, if left untreated, leads to death in 95% of the cases1. These protozoa are obligate intracellular parasites of lymphoid organs such as spleen, lymph nodes, bone marrow, and liver2. The disease manifests as intermittent fever, weight loss, hepatomegaly, major splenomegaly, and anemia1. Some laboratory findings of VL indicate that it is characterized by cytopenia and positive antibodies resembling an autoimmune rheumatic disease, especially systemic lupus erythematosus (SLE)3,4, a chronic disease characterized by multisystem inflammation of unknown cause5.

It is estimated that there are 50,000 to 90,000 cases annually of VL worldwide, of which 90% occur in seven countries, including Brazil1. According to data from Sistema de Informação de Agravos de Notificação (Brazil’s Information System for Notifiable Diseases; SINAN) from 2015 to 2016, 6,489 new cases were registered in the country in 22 of the 27 federative units. Santa Catarina was one of the five units without an autochthonous case recorded6.

CASE REPORT

This case involves a 53-year-old male patient from Florianópolis, Santa Catarina, residing in the Saco dos Limões neighborhood, who worked as a painter and went fishing as a leisure activity. In his house, he had two dogs without veterinary supervision. He denied traveling in recent years and making any trip out of state.

He visited the Emergency Service of the Hospital Universitário Professor Polydoro Ernani de São Thiago (Professor Polydoro Ernani University Hospital of São Thiago) in June 2017, owing to a 2-week period of having a nightly fever of up to 38°C, myalgia, asthenia, productive cough with yellowish mucus, and weight loss of approximately 10 kg. He also reported knee and elbow arthralgia.

At the physical examination, he was emaciated and pale, with a flat, flaccid, and painful abdomen on palpation of the epigastrium. He had hepatosplenomegaly (14 cm hepatometry and palpable spleen 3 cm from the left costal border). He had no lymphadenopathy or skin lesions. The most frequent diseases in Santa Catarina were eliminated, including leptospirosis, tuberculosis, HIV, and viral hepatitis B and C. Serology was repeated after a period of a possible immunological window.

Abdominal tomography confirmed hepatosplenomegaly, with the spleen on its largest axis measuring 19.6 cm. Laboratory tests revealed pancytopenia and elevated levels of C-reactive protein, lactate dehydrogenase, and hepatic markers (Table 1). The patient was discharged and followed up as an outpatient.

On his first follow-up visit, he presented worsening of asthenia, weight loss, and night fever. He reported a new episode of abdominal pain in the epigastric region. The examination showed hepatosplenomegaly, hepatometry of 16 cm, and palpable spleen 9.5 cm from the costal border. Laboratory results showed antinuclear factor (ANF) at 1:160 dilution with dense fine speckling and a cytoplasmic pattern, polyclonal hypergammaglobulinemia, pancytopenia with lymphopenia, and significant complement consumption and were positive for rheumatoid factor (RF), anti-cyclic citrullinated peptide (anti-CCP) antibody, and cryoglobulins; a direct Coombs test was also positive (Table 1).

TABLE 1: Laboratory exams. 

Exam Reference value Results
Hemoglobin, g/dl 13.2-18 9.1
Hematocrit 39-51% 28.5%
Leukocytes, /mm3 3800-11,000 2550
Segmented, /mm3 1700-7500 1453.5
Lymphocytes, /µl 1000-3500 561
Monocytes, /µl 200-920 127.5
Eosinophils, /µl 20-670 0
Basophils, /µl 0-130 25.5
Bands 0-5% 11%
Platelets, /mm3 150,000-440,000 86,000
C-reactive protein, mg/L ≤3 685
Lactate dehydrogenase, µ/L 81-234 845
Aspartate aminotransferase, µ/L 10-40 789
Alanine aminotransferase, µ/L 12-78 196
Rheumatoid factor, IU/ml <15 292
Anti-CCP, U Negative (<20) 46
Complement proteins
C3, mg/dl 90-180 62
C4, mg/dl 10-40 7.8
IgG, mg/dl 694-1618 3600
β2-Microglobulin, ng/ml 609-2164 7367
Protein electrophoresis 10.3-18.2% Hypergammaglobulinemia (44.2%)

CCP: anti-cyclic citrullinated peptide.

The diagnostic hypotheses at that time were autoimmune disease or lymphoma. Therefore, bone marrow aspiration was performed in the presence of persistent pancytopenia, with visualization of the amastigote form of Leishmania, confirming the diagnosis of VL via myelogram. In addition, test results showed a positive polymerase chain reaction for Leishmania infantum, reactive indirect immunofluorescence reaction at 1:640 dilution, and a positive culture.

Considering the absence of previous autochthonous visceral leishmaniasis in Santa Catarina, and since the patient denied recent trips, this is the first reported case of autochthonous VL in Santa Catarina according to the Municipal Health Secretariat and the State Epidemiological Surveillance Department. In addition to the epidemiological importance, this is a lupus-like condition, presenting with consumption of complement, pancytopenia with lymphopenia, hypergammaglobulinemia, a positive direct Coombs test, and ANF.

From the time of diagnosis, treatment with liposomal amphotericin B at 4 mg/kg/day was initiated owing to the age of the patient and the clinical and laboratory findings, which reduced the hepatomegaly and splenomegaly, improved the patient’s general state, and reduced the inflammatory markers. He was discharged in August 2017 with an afebrile disposition and was asymptomatic.

DISCUSSION

There are reports in the literature that leishmaniasis can mimic or trigger an autoimmune disease such as autoimmune hepatitis, systemic lupus erythematosus and rheumatoid arthritis (RA)7. The present case involves a patient with VL who presented with clinical and laboratory characteristics of SLE and some particularities of RA.

Autoimmune phenomena in VL have been described for a long time. In 1983, a prospective study was conducted in Rio de Janeiro to evaluate immunological phenomena of VL. Serum samples from 17 patients with a diagnosis of kala-azar were collected, in which were observed a significant increase in serum IgG and IgM, high levels of RF, anti-DNA positivity, ANF, anti-basal membrane antibodies, and anti-Sm antibodies8.

The mechanisms involved in the pathophysiology of this autoantibody production are not yet fully understood9. There is evidence that they are related to the activation of polyclonal B cells due to a decrease in regulatory T cell activity. Another possible mechanism would be the production of autoantigens in response to a cross-reaction between the parasite and host tissue antigens7,8. Notably, the patient had high titers of serum IgG, hypergammaglobulinemia, and increased β2-microglobulin, suggesting extensive activation of B cells.

The patient in this report was positive for RF and anti-CCP. RF has already been described in VL, but anti-CCP is not commonly reported. It should be noted that anti-CCP has 95% specificity for RA. A 2007 Brazilian study investigated the prevalence of anti-CCP in 10 patients with VL, demonstrating positive results in three of them. The study concluded that sporadic production of anti-CCP is an autoimmune feature of VL that may be caused by citrullination of host proteins during Leishmania infection9.

Consumption of C3 and C4, as observed in the patient in this study (Table 1), is seen in 50% of the cases10. However, in a review of the literature analyzing seven articles on VL mimicking SLE conducted by Santana et al. in 2015, only one described complement consumption in patients with VL11.

Clinical manifestations such as decreased general status, asthenia, weight loss, fever, splenomegaly, and pericardial effusion associated with laboratory data such as complement consumption, ANF positivity, a positive direct Coombs test, hypergammaglobulinemia, and pancytopenia are clinical and immunological changes related to SLE; however, as described above, they may also be present in patients with VL. Therefore, these data indicate that, in addition to SLE, VL should also be considered even in cases with negative epidemiology. In addition, although less frequently reported, VL may present as an opportunistic disease in immunocompromised patients with SLE, and thus, this differential diagnosis should be considered12.

Differentiating VL from autoimmune diseases can be challenging, especially when there is no positive epidemiology; however, it is of paramount importance as a misdiagnosis in patients who receive immunosuppressive treatments can lead to fatal consequences.11 Therefore, after this first described case of VL in the Santa Catarina, Brazil, it is suggested that the possibility of VL be considered in patients with lupus-like symptoms, especially before administering immunosuppressive drugs.

REFERENCES

1. World Health Organization (WHO). Leishmaniasis. (Accessed 2017 October 01) Available at Available at http://www.who.int/mediacentre/factsheets/fs375/en/ [ Links ]

2. Herwaldt BL. Leishmaniasis. Lancet. 1999;354(9185):1191-9. doi: 10.1016/S0140-6736(98)10178-2. PubMed PMID: 10513726 [ Links ]

3. Voulgarelis M, Voulgari PV, Serelis J, Drosos AA, Skopouli FN. Visceral leishmaniasis resembling systemic lupus erythematosus. Clin Rheumatol. 2003;22(6):452-5. Epub 2003/10/31. doi: 10.1007/s10067-003-0773-7. PubMed PMID: 14677027. [ Links ]

4. Ossandon A, Bompane D, Alessandri C, Marocchi E, Conti F, Valesini G. Leishmania in SLE mimicking an exacerbation. Clin Exp Rheumatol. 2006;24(2):186-90. Epub 2006/06/10. PubMed PMID: 16762157. [ Links ]

5. Guzmán J, Cardiel MH, Arce-Salinas A, Sánchez-Guerrero J, Alarcón-Segovia D. Measurement of disease activity in systemic lupus erythematosus. Prospective validation of 3 clinical indices. J Rheumatol. 1992;19(10):1551-8. PubMed PMID: 1464867. [ Links ]

6. Ministério da Saúde, Secretaria de Vigilância em Saúde, Sistema de Informação de Agravos de Notificação. Casos confirmados de Leishmaniose Visceral, Brasil, Grandes Regiões e Unidades Federadas. 1990 a 2016. (Acessado em Setembro de 2017). Disponível em: Disponível em: http://portalarquivos.saude.gov.br/images/pdf/2017/setembro/14/LV-Casos.pdf [ Links ]

7. Tunccan OG, Tufan A, Telli G, Akyürek N, Pamukçuoğlu M, Yılmaz G, et al. Visceral leishmaniasis mimicking autoimmune hepatitis, primary biliary cirrhosis, and systemic lupus erythematosus overlap. Korean J Parasitol. 2012;50(2):133-6. Epub 2012/05/24. doi: 10.3347/kjp.2012.50.2.133. PubMed PMID: 22711924; PubMed Central PMCID: PMCPMC3375451. [ Links ]

8. Galvão-Castro B, Sá Ferreira JA, Marzochi KF, Marzochi MC, Coutinho SG, Lambert PH. Polyclonal B cell activation, circulating immune complexes and autoimmunity in human american visceral leishmaniasis. Clin Exp Immunol. 1984;56(1):58-66. PubMed PMID: 6424987; PubMed Central PMCID: PMCPMC1535977. [ Links ]

9. Atta AM, Carvalho EM, Jeronimo SM, Sousa Atta ML. Serum markers of rheumatoid arthritis in visceral leishmaniasis: rheumatoid factor and anti-cyclic citrullinated peptide antibody. J Autoimmun. 2007;28(1):55-8. Epub 2007/01/30. doi: 10.1016/j.jaut.2006.12.001. PubMed PMID: 17257811. [ Links ]

10. Liberopoulos E, Kei A, Apostolou F, Elisaf M. Autoimmune manifestations in patients with visceral leishmaniasis. J Microbiol Immunol Infect. 2013;46(4):302-5. Epub 2012/04/17. doi: 10.1016/j.jmii.2012.01.016. PubMed PMID: 22516744. [ Links ]

11. Santana IU, Dias B, Nunes EA, Rocha FA, Silva FS, Santiago MB. Visceral leishmaniasis mimicking systemic lupus erythematosus: Case series and a systematic literature review. Semin Arthritis Rheum. 2015;44(6):658-65. Epub 2014/12/29. doi: 10.1016/j.semarthrit.2014.12.004. PubMed PMID: 25704907. [ Links ]

12. Fernández-Guerrero ML, Aguado JM, Buzón L, Barros C, Montalbán C, Martín T, et al. Visceral leishmaniasis in immunocompromised hosts. Am J Med. 1987;83(6):1098-102. PubMed PMID: 3332567. [ Links ]

Received: June 07, 2018; Accepted: October 13, 2018

Corresponding author: Greyce Cristine Lisboa Bueno. e-mail:greycelisboa@gmail.comOrcid: 0000-0001-8862-6566

Conflict of Interest: The authors declare that there is no conflict of interest.