Case ReportLeptospirosis and pancytopenia: two case reports and review of the literature
Introduction
Leptospirosis is a spirochetal zoonosis caused by Leptospira interrogans, usually transmitted to humans through contaminated water or direct exposure to the urine or tissues of infected animals. The clinical spectrum of the disease varies from a subclinical infection of a self-limited febrile episode to a severe illness (Weil's disease) and multiple organ dysfunction syndrome.1 However, leptospirosis may rarely occur with erythroid hypoplasia2 and/or pancytopenia.3, 4 In this study, two cases of leptospirosis presented with pancytopenia as the prevailing manifestation, are reported. In addition, the presence of pancytopenia in leptospirosis is reviewed.
A 64-year-old previously healthy man (cabinetmaker-farmer) was admitted in our department due to severe thrombocytopenia. The patient was also claimed for mild weakness, fatigue, lumbar pain and arthralgias of the lower and upper extremities. One-month ago he had experienced painless haematuria that lasted 24 h, while 15 days before admission an influenza-like syndrome had preceded, with fever up to 39 °C, non-productive cough and severe pain of the major joints without arthritis that receded within 2 days. On admission he was pale, without fever and well oriented without any rash or suffusion of the conjunctiva. Vital signs were normal and the physical examination was unremarkable. Past medical history was not contributory.
Laboratory investigation on admission showed: normochromic–normocytic anaemia with haematocrit 31.4%, haemoglobin 10.0 g/dl, reticulocytes 3×1010/l, leukocytes 3.3×109/l with 1.0×109/l neutrophils, and severe thrombocytopenia (platelets 14×109/l). Peripheral blood smear and biochemical markers were within normal with the exceptions of creatinine (1.34 mg/dl), urea (64.8 mg/dl), lactate dehydrogenase (252 U/l), creatinine kinase (CPK; 308 U/l) and total bilirubin 2.0 mg/dl. Urinalysis revealed haemoglobin (3+), 10–15 red blood cells/HPF, 1–2 white blood cells/HPF and no casts. Electrocardiography and chest X-ray were normal.
Direct Coombs test was negative and coagulation screen was normal. Concentrations of serum folate, vitamin B12 and ferritin were also within normal limits. Rheumatoid factor was undetectable and consecutive bacterial cultures of blood and urine were negative. Bone marrow biopsy and bone marrow aspiration were performed that revealed severe bone marrow hypoplasia with exclusive predominance of lipocytes (Fig. 1). Immunophenotype of peripheral blood was normal and immunological tests including anti-platelet antibodies were negative. Marrow cultures tested negative for tuberculosis bacillus, salmonellosis and brucellosis. Moreover, viral examination revealed negative serology for hepatitis A, B, C, coxsackie, echo, herpes simplex virus, human immunodeficiency virus, cytomegalovirus, Epstein–Barr and parvovirus. In contrast, IgM antibodies to Leptospira tested positive by a commercially available enzyme-linked immunosorbent assay (Leptospira IgM ELISA; PANBIO Inc., Columbia, MD, U.S.A.; cut-off of the assay: 9 U/ml) with increasing titre during a week period (45 U/ml initially and 80 U/ml 7 days later; both strong positive results).
A diagnosis of acute leptospirosis was considered and the patient was treated with penicillin 4 million units/6 h intravenously. It should be noted, that after the initiation of penicillin therapy, a Jarisch–Herxheimer reaction occurred with fever up to 39.5 °C in association with rigors. He was finally discharged from our hospital after 18 days of hospitalisation in a very good health with obvious improvement of biochemical and haematological parameters. A second bone marrow biopsy was performed 1 month later that revealed prominent erythropoeisis, normal morphology of megakaryocytes and markedly left-shifted myeloid series (Fig. 2).
A previous healthy 70-year-old man (farmer) was admitted in our department because of a 6-day history of high fever (40.5 °C) associated with confusion, chills, headache, anorexia, nausea, diffuse myalgias and severe pain of the major joints without any manifestation of arthritis. He was suffered from diabetes mellitus type II and psoriasis. On presentation, the patient's temperature was 39.1 °C, heart rate was 118 bpm, respiratory rate was 25 breaths per minute, blood pressure 115/70 mmHg and oxygen saturation 96%. He was well oriented, anicteric with significant conjunctival injection and extended skin lesions due to psoriasis on both legs but without petechiae. The rest physical examination was unremarkable.
Laboratory work-up on admission showed: haematocrit 31.2%, haemoglobin 10.1 g/dl, reticulocytes 4.34×1010/l and severe thrombocytopenia with platelets 23×109/l. White blood cells were 3.4×109/l with neutrophils 3×109/l. Serum urea was 69 mg/dl, creatinine 1.36 mg/dl, glucose 148 mg/dl, lactate dehydrogenase 386 U/l, C-reactive protein was high (15.63 mg/dl) and CPK 172.6 U/l. Liver function tests were as follows: total bilirubin 0.74 mg/dl, aspartate aminotransferase (AST) 80 U/l (normal <40 U/l), alanine aminotrasferase (ALT) 57 U/l (normal <40 U/l), alkaline phosphatase (ALP) 136 U/l (normal <104 U/l) and γ-glutamyltranspeptidase (γ-GT) 105 U/l (normal <40 U/l). Urinalysis revealed specific gravity of 1.025, pH 5.5, blood 3+, 1–2 red blood cells/HPF, 2–4 white blood cells/HPF and coarse granular casts. Electrocardiography and chest X-ray were normal. Serial bacterial cultures of blood and urine were negative and ultrasound of the upper abdomen was normal. Investigations for hepatitis A, B, C, coxsackie, echo, herpes simplex virus, human immunodeficiency virus, cytomegalovirus, Epstein–Barr and parvovirus were unrevealing. Bone marrow aspiration revealed hypoplastic bone marrow with extremely low number of megakaryocytes. On the second day of hospitalisation the patient developed diffuse petechiae on the extremities with platelet counts 17×109/l. Screening for disseminated intravascular coagulation (DIC) was negative but investigation for IgM antibodies against to Leptospira spp. revealed a mild positive result (20 U/ml by ELISA, which is near above the cut-off of this assay). Intravenous administration of penicillin (4 million units/6 h) was started because of the clinical and laboratory findings compatible with leptospirosis.
After 6 days of hospitalisation the patient had no fever. On the 10th day after admission (16th from the onset of the disease) the titre of IgM antibodies against to Leptospira spp. was 100 U/ml by the same commercial ELISA kit (strong positive result). The patient was finally discharged after 15 days of hospitalisation in a very good health and normal haematological and biochemical tests. On the day of discharge, a second bone marrow aspiration was performed that showed hyperplastic bone marrow with increased number of erythroid and myeloid series as well as increased number of megakaryocytes of normal morphology.
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Discussion
In this case study, two patients with severe transient bone marrow aplasia due to acute infection from Leptospira are presented. Pancytopenia is actually a very rare clinical manifestation of severe leptospirosis. Similar haematological manifestations have been described in a few previous reports.2, 3 Interestingly, Bishara et al. reported an incidence of pancytopenia as high as 28% among patients from Israel suffering from leptospirosis.4 On the contrary, isolated thrombocytopenia is observed
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