Seminars in Arthritis and Rheumatism 45 (2015) e3–e4
Contents lists available at ScienceDirect
Seminars in Arthritis and Rheumatism journal homepage: www.elsevier.com/locate/semarthrit
A case of leishmaniasis with a lupus-like presentation Dear Editor, We have read the article “Visceral leishmaniasis mimicking systemic lupus erythematosus: Case series and a systematic literature review” written by Santana et al. [1] with great interest. They have reported a case series of visceral leishmaniasis (VL) with clinical findings in acccordance with systemic lupus erythematosus (SLE). They explained that in endemic areas for visceral leishmaniasis, the diagnosis or exacerbation of SLE may be problematic and some characteristics like massive splenomegaly, arthritis, CRP measurements, serum complement levels, and antiLeishmania antibodies may help to distinguish each of these disorders. Systemic lupus erythematosus is an autoimmune disorder that can involve many tissues and lead to significant organ damage [2]. The presentation may be highly variable. After the diagnosis, most patients are obliged to long-time immunosuppressive drugs [3]. To avoid useless and life-threatening exposure to immunosuppressive treatments, we would like to present a similar adult case of VL mimicking SLE in a 6-month disease course and take attention on the subject that these patients may be misdiagnosed as SLE due to autoantibody production. A 21-year-old male patient was admitted with complaints of fever, fatigue, and weight loss continuing for 6 months. He said he initially received pneumonia treatment about 5 months before. Since his complaints were not relieved, he was referred to a thirdlevel healthcare center for a high erythrocyte sedimentation rate (ESR: 69 mm/h) and increased spleen size. On physical examination, right submandibular lymphadenopathy (LAP) was detected, which was approximately 1 cm in diameter. In that period, laboratory examination was as follows: hemoglobin (Hb): 11.1 g/dl, white blood cell (WBC): 3640/mm3, platelets (PLT): 210,000/mm3, blood urea nitrogen (BUN): 15 mg/dl, creatinine: 0.87 mmol/L, albumin: 3.4 g/dl, total protein: 8.89 g/dl, C-reactive protein: 122 mg/l, ferritin: 738 mg/dl, RF: 11.1 IU/mL, ANA IFA: 1/1000 in nucleolar pattern, direct Coombs (þ ), p-ANCA ( ), c-ANCA ( ), Brucella agglutination test ( ), hepatitis B and C tests were negative, lupus anticoagulant: 47.5 sec, C3 and C4 were in normal levels. Adenosine deaminase was 48 IU/mL but PPD was found anergic. In chest computerized tomography (CT), there were LAPs, the largest of which was 17 mm in short axis in left supraclavicular area, 15-mm LAP in both axillary fossa, and several mediastinal LAPs, the largest of which was 11 mm. In the lung parenchyma, fibrotic changes in the apex of the left lung and micronodular
DOI of original article: http://dx.doi.org/10.1016/j.semarthrit.2015.04.007 http://dx.doi.org/10.1016/j.semarthrit.2015.04.001 0049-0172/& 2015 Elsevier Inc. All rights reserved.
lesions were detected. The excisional biopsy of the supraclavicular LAP was reported as reactive lymphadenitis. The patient had undergone bone marrow aspiration and biopsy in which CD34 þ and CD117þ cells were counted as 3% on flow cytometry and biopsy was normocellular. Upper gastrointestinal endoscopy was performed to exclude malignancy, but it revealed nonerosive gastritis, mucosal bulging of gastric corpus giving rise to the thought of an external pressure or organomegaly. This was thought to be due to enlarged spleen. Rectosigmoidoscopy was normal. Echocardiography revealed a bicuspid aorta without any sign of infective endocarditis. Tuberculosis PCR, tularemia, and Coxiella burnetii tests were negative. The patient had a decayed tooth and it was pulled out. After consultation of rheumatology, since he had anemia, leukopenia, thrombocytopenia, ANA, and anticardiolipin antibody positivity, the patient was diagnosed as systemic lupus erythematosus as long as an infectious disease was excluded. Oral methylprednisolone (32 mg/day) and hydroxychloroquine (400 mg/day) treatment was started. The patient was referred to our tertiary hospital while taking this treatment for 1 month. In his clinical follow-up, the fever was up to 39.61, and sweating was accompanying the fever. It was more frequent in the evening and during the night. There was also a non-fever period lasting for 15 days in our clinical observation. He had fatigue, anorexia, and impaired oral intake. He expressed 7 kg weight loss from 62 kg in the last 6 months. He had bone pain in the shoulders, back, and legs for 2 weeks. There was no family history of any rheumatic disease. In physical examination, he was in moderate general medical condition, conscious, oriented, and cooperated. Cardiac examination was normal except mild tachycardia. He had a pale and moist skin, normal lung examination, Traube's space was closed, and spleen was passing 3 cm through the costal arch during deep inspiration. No LAP was detected. There was no evidence of active arthritis. Muscle strength was normal. Laboratory examination was as follows: Hb: 11 g/dl, WBC: 2570/mm3, PLT: 88,000/mm3, serum glucose: 85 mg/dl, BUN: 24 mg/dl, creatinine: 0.73, uric acid: 4.4 mg/dl, liver function tests were normal, total protein: 8.35 mg/dl, albumin: 3.18 mg/dl, LDH: 211 mg/dl, and all electrolytes were normal. ESR was 105 mm/h, CRP: 126 mg/l, and ferritin: 1606 mg/dl. The urinalysis was normal and 24-h urinary protein was 238 mg. ANA test was positive in immunoflourecence assay, anticardiolipin IgG was 15.7 (upper limit 9), RF: 25.3 IU/ml, aPTT: 31.5, INR was normal, thyroid function tests, vitamin b12, and folic acid were within normal levels. Salmonella Gruber Widal test was negative. Beta 2 microglobuline was 0.503 mg/l (upper limit 0.25). Patient was investigated in terms of a possible lymphoproliferative disease again. In computerized tomography imaging, there were enlarged liver and spleen of 20 and 18 cm, respectively. Liver and spleen were in homogeneous appearance. There were paratracheal nonspecific
e4
M. Çakar et al. / Seminars in Arthritis and Rheumatism 45 (2015) e3–e4
visceral leishmaniasis (Fig.). Lyposomal amphotericin-B treatment was started, and complete recovery was achieved after three weeks of treatment. There are some mechanisms that VL may lead to autoreactivity and autoantibody formation [4]. First is by destructing host cells and releasing autoantigens. Second, leishmania may alter host immune response. Third, the infection may cause polyclonal B-cell activation. The final antibody production may mimic SLE in these patients. It has also been noted that there are cases of leishmaniasis diagnosed during biologic therapies for rheumatoid arthritis or other rheumatologic diseases [5]. Therefore, as the diagnosis may be difficult, special attention should be paid on serological tests and bone marrow biopsy specimens in suspected cases. References
Fig. The 100 microscopic view of the bone marrow aspiration of the patient showing intracellular leishmania amastigotes.
LAPs and minimal nonspecific infiltration in the lung. Three consecutive blood and urine cultures that were obtained during the febrile episodes were negative. The serum protein electrophoresis were consistent with polyclonal gammopathy. We decided to re-examine bone marrow, because of findings suggestive for hemophagocytic lymphohistiocytosis such as marked hyperferritinemia (4601 mg/dl) and pancytopenia. In 3 areas, platelet phagocytosis was detected in bone marrow aspiration. As the patient’s general condition, persistent fever, pancytopenia, positivity of ANA, direct Coombs, anticardiolipin antibodies and lupus anticoagulant, elevated acute phase response in spite of the ongoing oral steroid therapy, and the previous lupus diagnosis were taken into account, a diagnosis of hemophagocytic lymphohistiocytosis secondary to SLE and 3-day pulse steroid with 1000-mg methylprednisolone was applied. After that, a general well-being and fever response was obtained. Meanwhile, on the examination of the bone marrow biopsy, Leishmania amastigotes were seen, and he was diagnosed as
[1] Santana IU, Dias B, Nunes EAS, Rocha FAC, da, Silva FSFS Jr, Santiago MB. Visceral leishmaniasis mimicking systemic lupus erythematosus: case series and a systematic literature review. Semin Arthritis Rheum 2014;S00490172:327–8, http://dx.doi.org/10.1016/j.semarthrit.2014.12.004. [2] Sutton EJ, Davidson JE, Bruce IN. The systemic lupus ınternational collaborating clinics (SLICC) damage index: a systematic literature review. Semin Arthritis Rheum 2013;43:352–61, http://dx.doi.org/10.1016/j.semarthrit.2013.05.003. [3] Merrill JT, Buyon JP, Utset T. A 2014 update on the management of patients with systemic lupus erythematosus. Semin Arthritis Rheum 2014;44:e1–2, http://dx.doi.org/10.1016/j.semarthrit.2014.09.013. [4] Sakkas LI, Boulbou M, Kyriakou D, Makri I, Sinani C, Germenis A, et al. Immunological features of visceral leishmaniasis may mimic systemic lupus erythematosus. Clin Biochem 2008;41:65–8, http://dx.doi.org/10.1016/j. clinbiochem.2007.10.008. [5] Cascio A, Iaria M, Iaria C. Leishmaniasis and biologic therapies for rheumatologic diseases. Semin Arthritis Rheum 2010;40:e3–5, http://dx.doi.org/10.1016/ j.semarthrit.2009.07.001.
Mustafa Çakar, MD, Muhammet Çınar, MD, Sedat Yılmaz, MD, Salıh Pay, MD Department of Rheumatology, Gulhane Medical Faculty Gen Tevfik Sag˘lam Caddesi, Etlik-Ankara 06100, Turkey E-mail addresses: [email protected] (M. Çakar) Selim Sayın, MD, Gökhan Özgür, MD Department of Hematology, Gulhane Medical Faculty Etlik-Ankara, Turkey
Contents lists available at ScienceDirect
Seminars in Arthritis and Rheumatism journal homepage: www.elsevier.com/locate/semarthrit
A case of leishmaniasis with a lupus-like presentation Dear Editor, We have read the article “Visceral leishmaniasis mimicking systemic lupus erythematosus: Case series and a systematic literature review” written by Santana et al. [1] with great interest. They have reported a case series of visceral leishmaniasis (VL) with clinical findings in acccordance with systemic lupus erythematosus (SLE). They explained that in endemic areas for visceral leishmaniasis, the diagnosis or exacerbation of SLE may be problematic and some characteristics like massive splenomegaly, arthritis, CRP measurements, serum complement levels, and antiLeishmania antibodies may help to distinguish each of these disorders. Systemic lupus erythematosus is an autoimmune disorder that can involve many tissues and lead to significant organ damage [2]. The presentation may be highly variable. After the diagnosis, most patients are obliged to long-time immunosuppressive drugs [3]. To avoid useless and life-threatening exposure to immunosuppressive treatments, we would like to present a similar adult case of VL mimicking SLE in a 6-month disease course and take attention on the subject that these patients may be misdiagnosed as SLE due to autoantibody production. A 21-year-old male patient was admitted with complaints of fever, fatigue, and weight loss continuing for 6 months. He said he initially received pneumonia treatment about 5 months before. Since his complaints were not relieved, he was referred to a thirdlevel healthcare center for a high erythrocyte sedimentation rate (ESR: 69 mm/h) and increased spleen size. On physical examination, right submandibular lymphadenopathy (LAP) was detected, which was approximately 1 cm in diameter. In that period, laboratory examination was as follows: hemoglobin (Hb): 11.1 g/dl, white blood cell (WBC): 3640/mm3, platelets (PLT): 210,000/mm3, blood urea nitrogen (BUN): 15 mg/dl, creatinine: 0.87 mmol/L, albumin: 3.4 g/dl, total protein: 8.89 g/dl, C-reactive protein: 122 mg/l, ferritin: 738 mg/dl, RF: 11.1 IU/mL, ANA IFA: 1/1000 in nucleolar pattern, direct Coombs (þ ), p-ANCA ( ), c-ANCA ( ), Brucella agglutination test ( ), hepatitis B and C tests were negative, lupus anticoagulant: 47.5 sec, C3 and C4 were in normal levels. Adenosine deaminase was 48 IU/mL but PPD was found anergic. In chest computerized tomography (CT), there were LAPs, the largest of which was 17 mm in short axis in left supraclavicular area, 15-mm LAP in both axillary fossa, and several mediastinal LAPs, the largest of which was 11 mm. In the lung parenchyma, fibrotic changes in the apex of the left lung and micronodular
DOI of original article: http://dx.doi.org/10.1016/j.semarthrit.2015.04.007 http://dx.doi.org/10.1016/j.semarthrit.2015.04.001 0049-0172/& 2015 Elsevier Inc. All rights reserved.
lesions were detected. The excisional biopsy of the supraclavicular LAP was reported as reactive lymphadenitis. The patient had undergone bone marrow aspiration and biopsy in which CD34 þ and CD117þ cells were counted as 3% on flow cytometry and biopsy was normocellular. Upper gastrointestinal endoscopy was performed to exclude malignancy, but it revealed nonerosive gastritis, mucosal bulging of gastric corpus giving rise to the thought of an external pressure or organomegaly. This was thought to be due to enlarged spleen. Rectosigmoidoscopy was normal. Echocardiography revealed a bicuspid aorta without any sign of infective endocarditis. Tuberculosis PCR, tularemia, and Coxiella burnetii tests were negative. The patient had a decayed tooth and it was pulled out. After consultation of rheumatology, since he had anemia, leukopenia, thrombocytopenia, ANA, and anticardiolipin antibody positivity, the patient was diagnosed as systemic lupus erythematosus as long as an infectious disease was excluded. Oral methylprednisolone (32 mg/day) and hydroxychloroquine (400 mg/day) treatment was started. The patient was referred to our tertiary hospital while taking this treatment for 1 month. In his clinical follow-up, the fever was up to 39.61, and sweating was accompanying the fever. It was more frequent in the evening and during the night. There was also a non-fever period lasting for 15 days in our clinical observation. He had fatigue, anorexia, and impaired oral intake. He expressed 7 kg weight loss from 62 kg in the last 6 months. He had bone pain in the shoulders, back, and legs for 2 weeks. There was no family history of any rheumatic disease. In physical examination, he was in moderate general medical condition, conscious, oriented, and cooperated. Cardiac examination was normal except mild tachycardia. He had a pale and moist skin, normal lung examination, Traube's space was closed, and spleen was passing 3 cm through the costal arch during deep inspiration. No LAP was detected. There was no evidence of active arthritis. Muscle strength was normal. Laboratory examination was as follows: Hb: 11 g/dl, WBC: 2570/mm3, PLT: 88,000/mm3, serum glucose: 85 mg/dl, BUN: 24 mg/dl, creatinine: 0.73, uric acid: 4.4 mg/dl, liver function tests were normal, total protein: 8.35 mg/dl, albumin: 3.18 mg/dl, LDH: 211 mg/dl, and all electrolytes were normal. ESR was 105 mm/h, CRP: 126 mg/l, and ferritin: 1606 mg/dl. The urinalysis was normal and 24-h urinary protein was 238 mg. ANA test was positive in immunoflourecence assay, anticardiolipin IgG was 15.7 (upper limit 9), RF: 25.3 IU/ml, aPTT: 31.5, INR was normal, thyroid function tests, vitamin b12, and folic acid were within normal levels. Salmonella Gruber Widal test was negative. Beta 2 microglobuline was 0.503 mg/l (upper limit 0.25). Patient was investigated in terms of a possible lymphoproliferative disease again. In computerized tomography imaging, there were enlarged liver and spleen of 20 and 18 cm, respectively. Liver and spleen were in homogeneous appearance. There were paratracheal nonspecific
e4
M. Çakar et al. / Seminars in Arthritis and Rheumatism 45 (2015) e3–e4
visceral leishmaniasis (Fig.). Lyposomal amphotericin-B treatment was started, and complete recovery was achieved after three weeks of treatment. There are some mechanisms that VL may lead to autoreactivity and autoantibody formation [4]. First is by destructing host cells and releasing autoantigens. Second, leishmania may alter host immune response. Third, the infection may cause polyclonal B-cell activation. The final antibody production may mimic SLE in these patients. It has also been noted that there are cases of leishmaniasis diagnosed during biologic therapies for rheumatoid arthritis or other rheumatologic diseases [5]. Therefore, as the diagnosis may be difficult, special attention should be paid on serological tests and bone marrow biopsy specimens in suspected cases. References
Fig. The 100 microscopic view of the bone marrow aspiration of the patient showing intracellular leishmania amastigotes.
LAPs and minimal nonspecific infiltration in the lung. Three consecutive blood and urine cultures that were obtained during the febrile episodes were negative. The serum protein electrophoresis were consistent with polyclonal gammopathy. We decided to re-examine bone marrow, because of findings suggestive for hemophagocytic lymphohistiocytosis such as marked hyperferritinemia (4601 mg/dl) and pancytopenia. In 3 areas, platelet phagocytosis was detected in bone marrow aspiration. As the patient’s general condition, persistent fever, pancytopenia, positivity of ANA, direct Coombs, anticardiolipin antibodies and lupus anticoagulant, elevated acute phase response in spite of the ongoing oral steroid therapy, and the previous lupus diagnosis were taken into account, a diagnosis of hemophagocytic lymphohistiocytosis secondary to SLE and 3-day pulse steroid with 1000-mg methylprednisolone was applied. After that, a general well-being and fever response was obtained. Meanwhile, on the examination of the bone marrow biopsy, Leishmania amastigotes were seen, and he was diagnosed as
[1] Santana IU, Dias B, Nunes EAS, Rocha FAC, da, Silva FSFS Jr, Santiago MB. Visceral leishmaniasis mimicking systemic lupus erythematosus: case series and a systematic literature review. Semin Arthritis Rheum 2014;S00490172:327–8, http://dx.doi.org/10.1016/j.semarthrit.2014.12.004. [2] Sutton EJ, Davidson JE, Bruce IN. The systemic lupus ınternational collaborating clinics (SLICC) damage index: a systematic literature review. Semin Arthritis Rheum 2013;43:352–61, http://dx.doi.org/10.1016/j.semarthrit.2013.05.003. [3] Merrill JT, Buyon JP, Utset T. A 2014 update on the management of patients with systemic lupus erythematosus. Semin Arthritis Rheum 2014;44:e1–2, http://dx.doi.org/10.1016/j.semarthrit.2014.09.013. [4] Sakkas LI, Boulbou M, Kyriakou D, Makri I, Sinani C, Germenis A, et al. Immunological features of visceral leishmaniasis may mimic systemic lupus erythematosus. Clin Biochem 2008;41:65–8, http://dx.doi.org/10.1016/j. clinbiochem.2007.10.008. [5] Cascio A, Iaria M, Iaria C. Leishmaniasis and biologic therapies for rheumatologic diseases. Semin Arthritis Rheum 2010;40:e3–5, http://dx.doi.org/10.1016/ j.semarthrit.2009.07.001.
Mustafa Çakar, MD, Muhammet Çınar, MD, Sedat Yılmaz, MD, Salıh Pay, MD Department of Rheumatology, Gulhane Medical Faculty Gen Tevfik Sag˘lam Caddesi, Etlik-Ankara 06100, Turkey E-mail addresses: [email protected] (M. Çakar) Selim Sayın, MD, Gökhan Özgür, MD Department of Hematology, Gulhane Medical Faculty Etlik-Ankara, Turkey
