|CLINICAL CASE REPORT
|Year : 2019 | Volume
| Issue : 2 | Page : 88-89
Weil syndrome causing autoimmune haemolytic anaemia
Rahul Sai Gangula, M Mukhyaprana Prabhu, Weena Stanley
Department of Medicine, Kasturba Medical College, Sharada Madhava Pai OPD Block, Manipal, Karnataka, India
|Date of Web Publication||7-Jan-2020|
M Mukhyaprana Prabhu
Department of Medicine, Kasturba Medical College, Sharada Madhava Pai OPD Block, Manipal, Karnataka
Source of Support: None, Conflict of Interest: None
Weil syndrome is a fulminant form of leptospirosis, usually caused by spirochetal organism Leptospira interrogans. It is characterized by icterus, petechial rashes over the body, signs of renal failure and hepatic failure. Anaemia is a usual manifes- tation of Leptospira infection, but autoimmune haemolytic anaemia is rare. We report a patient with autoimmune haemolytic anaemia following Leptospira infection, which was responsive to high-dose steroid therapy.
|How to cite this article:|
Gangula RS, Prabhu M M, Stanley W. Weil syndrome causing autoimmune haemolytic anaemia. Natl Med J India 2019;32:88-9
|How to cite this URL:|
Gangula RS, Prabhu M M, Stanley W. Weil syndrome causing autoimmune haemolytic anaemia. Natl Med J India [serial online] 2019 [cited 2020 Sep 20];32:88-9. Available from: http://www.nmji.in/text.asp?2019/32/2/88/275913
| Introduction|| |
Weil disease-associated, autoimmune-mediated vasculitis is a well-documented phenomenon. However, autoimmune-mediated anaemia is rarely documented or under-recognized. We report a patient with autoimmune haemolytic anaemia in Weil syndrome, which has previously been reported in only four cases in the medical literature.
| The Case|| |
A 50-year-old farmer came to our hospital with complaints of yellowish discolouration of his eyes for 10-15 days, fever and abdominal pain for 2 days, and breathlessness for 1 day. He described the fever as intermittent, low grade, and associated with chills and rigors. The abdominal pain was localized to the right lower quadrant and he had one episode of vomiting. The patient started having breathing difficulty for 1 day, even at rest. He had no previous illness and used to consume 90 ml of whisky daily for 3 years, which he had stopped 1 year ago.
At the time of admission, examination revealed-pulse rate 90/minute, blood pressure 130/80 mmHg in the right arm supine position, temperature 98.6 °F and respiratory rate 24/minute. He had icterus, bilateral crepitations in the infrascapular area, no use of his accessory muscles, tenderness over the right iliac fossa and no organomegaly. A provisional diagnosis of leptospirosis was made as the patient came from an area endemic for Leptospira infection. His laboratory investigations are shown in [Table 1].
He was empirically started on piperacillin and tazobactam, ceftriaxone and doxycycline. As there was progressive renal failure with septic acute tubular necrosis and rhabdomyolysis, haemodialysis was started. Doxycycline was stopped on day 4 as his liver function tests deteriorated. Despite 5 days of antibiotics, the patient was deteriorating clinically and due to poor oxygenation was intubated and connected to a mechanical ventilator.
Meropenem was added and ceftriaxone was continued. He started improving clinically, his oxygenation improved, his ventilatory assistance was decreased and weaning trial was conducted after the rapid shallow breathing index was calculated. He was then extubated and continued on oxygen supplementation. His Leptospira serology was positive for immunoglobulin M (IgM) antibodies.
The patient developed anaemia, which progressed slowly during his hospital stay with the haemoglobin decreasing from 12.7 g/dl to 5.5 g/dl. His peripheral smear was suggestive of spherocytes and evidence of haemolysis with fragmented red blood cells; lactate dehydrogenase (LDH) was elevated and the direct Coombs test was positive-suggestive of autoimmune haemolytic anaemia. Drug- induced haemolytic anaemia was unlikely as he was not on any drugs which would have caused it (antibiotics had been stopped about 10 days after admission). A vasculitis work-up was negative and there were no other manifestations of vasculitis. A cold agglutination test was not done as the patient was deteriorating. He was started on injectable corticosteroids following which his haemoglobin started improving. He was then changed to oral high- dose steroids. The patient improved with no further complications and no decrease in haemoglobin till his next follow-up after 1 month. The steroids were tapered over the following 6 weeks and patient has had no further relapses[Figure 1].
|Fidure 1: Graphical table with haemoglobin on the Y-axis and important events and time on the X-axis DCT direct Coombs test|
Click here to view
| Discussion|| |
Leptospirosis is a zoonotic disease, caused by genus Leptospira spirochetal infection.1 The most common species causing Weil disease in humans is Leptospira interrogans.  The clinical spectrum of Leptospira infection includes asymptomatic mild illness through fulminant Weil syndrome causing bleeding, renal and hepatic failure.1,2 Rhabdomyolysis, pulmonary haemorrhage, myocarditis, thrombotic microangiopathy, meningitis and cerebellitis are rare manifestations of leptospirosis. ,
Autoimmune haemolytic anaemia associated with leptospirosis is a well-documented phenomenon in animals. ,,,, However, human Leptospira infection triggering immune-mediated haemolytic anaemia is rare and only four case reports are available in the medical literature. ,,,
Anaemia is also an important usual manifestation in Leptospira infection. Initial studies led to the belief that suppression of erythropoiesis was the primary mechanism involved.  However, studies, which did sternal biopsy, indicate that there was moderate activation of erythropoiesis, which contradicted the traditional belief. ,, These studies proved that anaemia in leptospirosis did not impair functional ability of the bone marrow, but it was hyperproliferative normoblastic haematopoiesis.  They concluded that low glucose-6-phosphate dehydrogenase might be a prognostic criterion for developing an anaemic syndrome.  They also concluded that anaemia in the acute phase of illness was primarily due to erythrocyte haemolysis, while anaemia in the latter part of the illness was mostly due to renal failure.  There is some evidence that plasmapheresis improves the outcome, supporting evidence of an immune-mediated pathology. ,
Our patient developed Weil syndrome acutely and so it was unlikely that renal failure was causing anaemia.15 In addition to the evidence of haemolysis in the peripheral smear, there was elevated LDH, spherocytes in the peripheral smear, positive direct Coombs test and elevated reticulocyte count and index, which were suggestive of autoimmune-mediated haemolysis. The patient was initially started on a high dose of steroids (1 mg/kg/day) and he responded well. Hence, intravenous immunoglobulin (IvIg) was not started, as done in some previous studies. Patients might develop immune-mediated haemolysis in some leptospiral infections for which immunosuppressants, IvIg or plasmapheresis may be the ideal choice. 
| References|| |
Plank R, Dean D. Overview of the epidemiology, microbiology, and pathogenesis of Leptospira
spp. in humans. Microbes Infect
Rajapakse S, Rodrigo C, Balaji K, Fernando SD. Atypical manifestations of leptospirosis. Trans R Soc Trop Med Hyg
Smith BP, Armstrong JM. Fatal hemolytic anemia attributed to leptospirosis in lambs. J Am Vet Med Assoc
Lee SH, Kim S, Park SC, Kim MJ. Cytotoxic activities of Leptospira interrogans
hemolysin SphH as a pore-forming protein on mammalian cells. Infect Immun
Bhasin JL, Freeman MJ, Morter RL. Properties of a cold hemagglutin in associated with leptospiral hemolytic anemia of sheep. Infect Immun
Cordy DR, Jasper DE. The pathology of an acute hemolytic anemia of cattle in California associated with Leptospira
. J Am Vet Med Assoc
Russell CM. A hemolysin associated with leptospirae. J Immunol
Solmazgul E, Turhan V, Unver S, Demirci M, Nalbant S, Danaci M, et al.
A case of Weil's syndrome developing steroid resistant immune haemolytic anaemia. Scand J Infect Dis
Bowsher B, Callahan CW, Person DA, Ruess L. Unilateral leptospiral pneumonia and cold agglutinin disease. Chest
Zschiedrich S, Fischer KG. Severe Weil's syndrome complicated by hemolytic anemia. Int J Infect Dis
Trowbridge AA, Green JB 3rd, Bonnett JD, Shohet SB, Ponnappa BD, McCombs WB 3rd, et al.
Hemolytic anemia associated with leptospirosis. Morphologic and lipid studies. Am J Clin Pathol
Somers CJ, Al-Kindi S, Montague S, O'Connor R, Murphy PG, Jeffers M, et al.
Erythroid hypoplasia associated with leptospirosis. J Infect
Avdeeva MG, Mo-´sova DL, Kachanov AV. Bone marrow hematopoiesis in leptospirosis and its role in anemia pathogenesis. Klin Lab Diagn
Avdeeva MG, Mo-´sova DL, Gorodin VN, Kostomarov AM, Zotov SV, Cherniavskaia OV, et al.
The role glucose-6-phosphate dehydrogenase in pathogenesis of anemia in leptospirosis. Klin Med (Mosk)
Avdeeva MG, Mo-´sova DL, Zentsova OA, Kostomarov AM. Hematological parameters in characterization of anemia in leptospirosis. Klin Lab Diagn
Landini S, Coli U, Lucatello S, Bazzato G. Plasma exchange in severe leptospirosis. Lancet
Tse KC, Yip PS, Hui KM, Li FK, Yuen KY, Lai KN, et al.
Potential benefit of plasma exchange in treatment of severe icteric leptospirosis complicated by acute renal failure. Clin Diagn Lab Immunol
Packman CH. The clinical pictures of autoimmune hemolytic anemia. Transfus Med Hemother