Aging Clin Exp Res DOI 10.1007/s40520-014-0219-x
CASE REPORT
An unusual case of pancytopenia in a nonagenarian: visceral leishmaniasis Jose´ M. Ramos • Antonio Tello • Rafael Leo´n • Esperanza Merino
Received: 27 December 2013 / Accepted: 2 April 2014 Ó Springer International Publishing Switzerland 2014
Abstract Older patients referred for further investigation of pancytopenia is common in internal medicine and geriatric clinics and it is important to consider a wide range of underlying diagnoses. We present an unusual case of febrile pancytopenia in a nonagenarian who was diagnosed with visceral leishmaniasis. This is a rare and unusual diagnosis in nonagenarians, although the leishmaniasis is endemic on the Mediterranean coast of Spain. It is important to identify it because it is treatable and curable. Keywords Pancytopenia Visceral leishmaniasis Nonagenarian
Case report A 93-year-old male had a 1-month history of progressive physical impairment and weight loss. The family also reported fever. He had an extensive medical history including ischemic heart disease, chronic kidney disease, hypertension, and diabetes mellitus type 2. He lived in the countryside near the city of Alicante (Mediterranean Coast of Spain). His daughter was his neighbor and lived in the J. M. Ramos (&) A. Tello R. Leo´n Department of Internal Medicine, Servicio de Medicina Interna, Hospital General Universitario de Alicante, C/Pintor Baeza, 12, 03010 Alicante, Spain e-mail: [email protected]
house next to him. She had a dog, which was diagnosed with leishmaniasis 3 months prior to the patient’s admittance. On physical examination, our patient was frail with a weight of 46.5 kg, pale and hepatosplenomegaly was suspected. Blood tests revealed anemia with hemoglobin 7.1 g/dl and MCV 93.4 fl, leukopenia with white blood cell count 1.8 9 109/l (neutrophils 1.0 9 109/l and lymphocytes, 0.8 9 109/l), and thrombocytopenia with 84 9 109/l platelets. Main differential diagnoses included oncological or hematological diseases. Computerized tomography confirmed hepatosplenomegaly. Leishmania serology was positive by immunofluorescence ([1/640). An aspiration of bone marrow was performed. Upon cytological examination, the bone marrow tested negative for Leishmania amastigotes. The culture in Novy–MacNeal–Nicolle medium for Leishmania was negative. Leishmania DNA was extracted, and amplification was attempted using PCR, which proved to be positive. The patient was treated with a dose of 21 mg/kg of liposomal amphotericin B. Despite the appearance of complications during treatment, with worsening chronic kidney failure and polyarthritis caused by uric acid, the treatment was successful; fever and hepatosplenomegaly were eliminated and white blood cell, hemoglobin and platelets levels increased. Consequently, the patient’s daughter tested positive in a Leishmania serology (1/160), without disease.
J. M. Ramos A. Tello Department of Medicine, Miguel Herna´ndez University of Elche, San Juan Campus, Alicante, Spain
Discussion
E. Merino Infectious Diseases Unit, Hospital General Universitario de Alicante, Alicante, Spain
Leishmaniasis is a parasitic endemic disease and is recognized as one of the neglected tropical diseases. Up to 30
123
Aging Clin Exp Res
species of Leishmania genus are known, but L. donovani, L. infantum and L. chagasi are the most commonly implicated. Transmission is by phlebotomine sand flies from reservoirs. There are two main clinical syndromes: cutaneous leishmaniasis, and visceral leishmaniasis (VL). VL affects internal organs such as the liver, the spleen, and bone marrow with a significant mortality rate if untreated. European zoonotic VL affects mainly children and young adults [1–3]. However, during the last few decades, the majority of cases have occurred in adult patients with HIV infection or symptomatic acquired immunodeficiency syndrome (AIDS), in organ transplant recipients with immunosuppression, in malnutrition illnesses and neoplastic disorders, especially hematological malignancies, and in subjects undergoing immunosuppressive therapy including anti-TNF drugs [1–3]. The presence of antibodies can help to diagnose VL. The presence of antibodies in asymptomatic patients increases with age. The presence of antibodies should be induced to perform a molecular marker to detect symptomatic infection, as in our case. The treatment of leishmaniasis remains complex. In developed countries, liposomal amphotericin B remains the treatment of choice [1]. In the Mediterranean VL 18 mg/kg of liposomal amphotericin B is considered enough to treat the disease. In our report, the patient was treated with a dose of 21 mg/kg. In our hospital, from January 1998 to August 2013, 77 patients were diagnosed with VL, and only three cases were geriatric patients (67 and 69-year-old and this case report) (Table 1). In several series of VL reported in endemic areas, the cases ranged from infants to elderly people [2, 3]. VL was commonly found in patients younger than 90 years of age [3]. There has been one case recorded of an 88-year-old British patient with VL acquired in Spain [4]. However, as far as we know, case reports in nonagenarian patients have not been reported. The most profound consequence of immunosenescence or immune aging with respect to human health is the increased susceptibility to infectious diseases [5]. Immunosenescence affects adaptive and innate response. Our patients presented elements indicating an immunosenescence such as leukopenia and lymphopenia; we did not, however, measure any elementary changes produced in immune aging such as reduced CD4 cells with a decreased CD4/CD8 rate. It is possible to study other immunosenescence data, but it is used more commonly for immunological research (phagocytic chemotaxis capability of neutrophils and macrophages, cytokine synthesis, numbers of dendritic cells, memory/naı¨ve B cell count, measure of NK-cell cytotoxicity and so on). Even though our study showed that the majority of VL cases occurred in patients between 15 and 64-year-old, we must consider that we have an aging population and that patients are living in endemic areas with zoonotic VL. It is
123
Table 1 Main characteristics of patients with visceral leishmaniasis from 1998 to 2013 N Median age (range)
%
33 (1–93)
Age group B14 years
12
15.6
15–64 years
62
80.5
C65 years
3
3.9
62 15
80.5 19.5
HIV infection
52
67.2
Immunosuppression conditiona
6
7.8
Sex Male Female Underlying conditions
Immunosenescence Total cases
1 77
1.3 100
a
Transplantation (n =3), treatment with immunosuppressive drugs (n = 2) and common immunodeficiency (n = 1)
probable that VL in nonagenarians will be more common in the future [5]. This is a rare and unusual diagnosis in a nonagenarian, although VL is endemic on the Mediterranean coast of Spain. Immunosenescence can predispose the patient to VL after contact with parasites. Awareness of VL is essential for geriatricians and internal medicine physicians to ensure its correct diagnosis and prompt treatment. Moreover, VL can be cured with the correct treatment.
Conflict of interest On behalf of all authors, the corresponding author states that there is no conflict of interest.
References 1. Pagliano P, Rossi M, Rescigno C et al (2003) Mediterranean visceral leishmaniasis in HIV-negative adults: a retrospective analysis of 64 consecutive cases (1995–2001). J Antimicrob Chemother 52:264–268. doi:10.1093/jac/dkg340 2. Cenderello G, Pasa A, Dusi A et al (2013) Varied spectrum of clinical presentation and mortality in a prospective registry of visceral leishmaniasis in a low endemicity area of Northern Italy. BMC Infect Dis 13:248. doi:10.1186/1471-2334-13-248 3. Gil-Prieto R, Walter S, Alvar J, de Miguel AG (2011) Epidemiology of leishmaniasis in Spain based on hospitalization records (1997–2008). Am J Trop Med Hyg 85:820–825. doi:10.4269/ ajtmh.2011.11-0310 4. McCusker L, Platt J (2012) An unusual case of anaemia in an octogenarian. Age Ageing 2012(41):696–698. doi:10.1093/ageing/ afs075 5. Ramos JM, Sa´nchez-Martı´nez R, Nieto F et al (2013) Characteristics and outcome in nonagenarians admitted in general internal medicine and other specialties. Eur J Intern Med 24:740–744. doi:10.1016/j.ejim.2013.07.003
CASE REPORT
An unusual case of pancytopenia in a nonagenarian: visceral leishmaniasis Jose´ M. Ramos • Antonio Tello • Rafael Leo´n • Esperanza Merino
Received: 27 December 2013 / Accepted: 2 April 2014 Ó Springer International Publishing Switzerland 2014
Abstract Older patients referred for further investigation of pancytopenia is common in internal medicine and geriatric clinics and it is important to consider a wide range of underlying diagnoses. We present an unusual case of febrile pancytopenia in a nonagenarian who was diagnosed with visceral leishmaniasis. This is a rare and unusual diagnosis in nonagenarians, although the leishmaniasis is endemic on the Mediterranean coast of Spain. It is important to identify it because it is treatable and curable. Keywords Pancytopenia Visceral leishmaniasis Nonagenarian
Case report A 93-year-old male had a 1-month history of progressive physical impairment and weight loss. The family also reported fever. He had an extensive medical history including ischemic heart disease, chronic kidney disease, hypertension, and diabetes mellitus type 2. He lived in the countryside near the city of Alicante (Mediterranean Coast of Spain). His daughter was his neighbor and lived in the J. M. Ramos (&) A. Tello R. Leo´n Department of Internal Medicine, Servicio de Medicina Interna, Hospital General Universitario de Alicante, C/Pintor Baeza, 12, 03010 Alicante, Spain e-mail: [email protected]
house next to him. She had a dog, which was diagnosed with leishmaniasis 3 months prior to the patient’s admittance. On physical examination, our patient was frail with a weight of 46.5 kg, pale and hepatosplenomegaly was suspected. Blood tests revealed anemia with hemoglobin 7.1 g/dl and MCV 93.4 fl, leukopenia with white blood cell count 1.8 9 109/l (neutrophils 1.0 9 109/l and lymphocytes, 0.8 9 109/l), and thrombocytopenia with 84 9 109/l platelets. Main differential diagnoses included oncological or hematological diseases. Computerized tomography confirmed hepatosplenomegaly. Leishmania serology was positive by immunofluorescence ([1/640). An aspiration of bone marrow was performed. Upon cytological examination, the bone marrow tested negative for Leishmania amastigotes. The culture in Novy–MacNeal–Nicolle medium for Leishmania was negative. Leishmania DNA was extracted, and amplification was attempted using PCR, which proved to be positive. The patient was treated with a dose of 21 mg/kg of liposomal amphotericin B. Despite the appearance of complications during treatment, with worsening chronic kidney failure and polyarthritis caused by uric acid, the treatment was successful; fever and hepatosplenomegaly were eliminated and white blood cell, hemoglobin and platelets levels increased. Consequently, the patient’s daughter tested positive in a Leishmania serology (1/160), without disease.
J. M. Ramos A. Tello Department of Medicine, Miguel Herna´ndez University of Elche, San Juan Campus, Alicante, Spain
Discussion
E. Merino Infectious Diseases Unit, Hospital General Universitario de Alicante, Alicante, Spain
Leishmaniasis is a parasitic endemic disease and is recognized as one of the neglected tropical diseases. Up to 30
123
Aging Clin Exp Res
species of Leishmania genus are known, but L. donovani, L. infantum and L. chagasi are the most commonly implicated. Transmission is by phlebotomine sand flies from reservoirs. There are two main clinical syndromes: cutaneous leishmaniasis, and visceral leishmaniasis (VL). VL affects internal organs such as the liver, the spleen, and bone marrow with a significant mortality rate if untreated. European zoonotic VL affects mainly children and young adults [1–3]. However, during the last few decades, the majority of cases have occurred in adult patients with HIV infection or symptomatic acquired immunodeficiency syndrome (AIDS), in organ transplant recipients with immunosuppression, in malnutrition illnesses and neoplastic disorders, especially hematological malignancies, and in subjects undergoing immunosuppressive therapy including anti-TNF drugs [1–3]. The presence of antibodies can help to diagnose VL. The presence of antibodies in asymptomatic patients increases with age. The presence of antibodies should be induced to perform a molecular marker to detect symptomatic infection, as in our case. The treatment of leishmaniasis remains complex. In developed countries, liposomal amphotericin B remains the treatment of choice [1]. In the Mediterranean VL 18 mg/kg of liposomal amphotericin B is considered enough to treat the disease. In our report, the patient was treated with a dose of 21 mg/kg. In our hospital, from January 1998 to August 2013, 77 patients were diagnosed with VL, and only three cases were geriatric patients (67 and 69-year-old and this case report) (Table 1). In several series of VL reported in endemic areas, the cases ranged from infants to elderly people [2, 3]. VL was commonly found in patients younger than 90 years of age [3]. There has been one case recorded of an 88-year-old British patient with VL acquired in Spain [4]. However, as far as we know, case reports in nonagenarian patients have not been reported. The most profound consequence of immunosenescence or immune aging with respect to human health is the increased susceptibility to infectious diseases [5]. Immunosenescence affects adaptive and innate response. Our patients presented elements indicating an immunosenescence such as leukopenia and lymphopenia; we did not, however, measure any elementary changes produced in immune aging such as reduced CD4 cells with a decreased CD4/CD8 rate. It is possible to study other immunosenescence data, but it is used more commonly for immunological research (phagocytic chemotaxis capability of neutrophils and macrophages, cytokine synthesis, numbers of dendritic cells, memory/naı¨ve B cell count, measure of NK-cell cytotoxicity and so on). Even though our study showed that the majority of VL cases occurred in patients between 15 and 64-year-old, we must consider that we have an aging population and that patients are living in endemic areas with zoonotic VL. It is
123
Table 1 Main characteristics of patients with visceral leishmaniasis from 1998 to 2013 N Median age (range)
%
33 (1–93)
Age group B14 years
12
15.6
15–64 years
62
80.5
C65 years
3
3.9
62 15
80.5 19.5
HIV infection
52
67.2
Immunosuppression conditiona
6
7.8
Sex Male Female Underlying conditions
Immunosenescence Total cases
1 77
1.3 100
a
Transplantation (n =3), treatment with immunosuppressive drugs (n = 2) and common immunodeficiency (n = 1)
probable that VL in nonagenarians will be more common in the future [5]. This is a rare and unusual diagnosis in a nonagenarian, although VL is endemic on the Mediterranean coast of Spain. Immunosenescence can predispose the patient to VL after contact with parasites. Awareness of VL is essential for geriatricians and internal medicine physicians to ensure its correct diagnosis and prompt treatment. Moreover, VL can be cured with the correct treatment.
Conflict of interest On behalf of all authors, the corresponding author states that there is no conflict of interest.
References 1. Pagliano P, Rossi M, Rescigno C et al (2003) Mediterranean visceral leishmaniasis in HIV-negative adults: a retrospective analysis of 64 consecutive cases (1995–2001). J Antimicrob Chemother 52:264–268. doi:10.1093/jac/dkg340 2. Cenderello G, Pasa A, Dusi A et al (2013) Varied spectrum of clinical presentation and mortality in a prospective registry of visceral leishmaniasis in a low endemicity area of Northern Italy. BMC Infect Dis 13:248. doi:10.1186/1471-2334-13-248 3. Gil-Prieto R, Walter S, Alvar J, de Miguel AG (2011) Epidemiology of leishmaniasis in Spain based on hospitalization records (1997–2008). Am J Trop Med Hyg 85:820–825. doi:10.4269/ ajtmh.2011.11-0310 4. McCusker L, Platt J (2012) An unusual case of anaemia in an octogenarian. Age Ageing 2012(41):696–698. doi:10.1093/ageing/ afs075 5. Ramos JM, Sa´nchez-Martı´nez R, Nieto F et al (2013) Characteristics and outcome in nonagenarians admitted in general internal medicine and other specialties. Eur J Intern Med 24:740–744. doi:10.1016/j.ejim.2013.07.003
