Journal of Postgraduate Medicine Medknow Publications and Staff Society of Seth GS Medical College and KEM Hospital, Mumbai, India ISSN: 0022-3859 EISSN: 0972-2823 Vol. 48, Num. 2, 2002, pp. 131-132

Journal of Postgraduate Medicine, Vol. 48, Issue 2, 2002 pp. 131-132

Leptospirosis Associated With Diffuse Alveolar Haemorrhage

Divate SA, Chaturvedi R, Jadhav NN, Vaideeswar P

Department of Pathology, Seth G. S. Medical College and K. E. M. Hospital, Parel, Mumbai - 400012, India.
Address for Correspondence: Smita Divate, MD, Department of Pathology, Seth G. S. Medical College and K. E. M. Hospital, Parel, Mumbai 400 012 E-mail : smitabijur@yahoo.com

Code Number: jp02043

A 48-year-old man presented with high grade fever with chills, cough with mucoid expectoration, occasional streaky haemoptysis, bilateral lower chest pain, progressive exertional breathlessness and oliguria of two days' duration. He also had haematemesis and malena one day prior to admission. Physical examination on admission revealed a feeble pulse, hypotension, tachypnoea, icterus, pallor and subconjunctival suffusion. Bilateral coarse crepitations were heard on examination of the respiratory system. He also had a mild hepatomegaly and altered sensorium. Investigations revealed haemoglobin concentration of 8.5 gm% and a total leucocyte count of 37,300/cmm with 92% neutrophils and 18% lymphocytes. His blood urea nitrogen was 200 mg%, serum creatinine 4.5 mg%, total bilirubin 23.0 mg%, direct bilirubin 16.0 mg%, serum alanine aminotransferase 1100 I.U./ml, serum aspartate aminotransferase 1072 I.U./ml. The prothrombin time and activated partial thromboplastin time were prolonged. The analysis of arterial blood gases revealed severe hypoxia with metabolic acidosis. Smears for malarial parasites and tests for human immunodeficiency virus and hepatitis B surface antigen were negative. Chest radiographs revealed bilateral diffuse ill-defined shadows. The microscopic agglutination test for leptospirosis was positive. The patient died within half an hour of admission. A complete autopsy was performed. External examination revealed an averagely built and nourished individual with icterus, pallor and subconjunctival suffusion. On gross examination the lungs were firm, plum coloured with pleural petechial haemorrh-ages. Other salient macroscopic findings were epicardial petechiae, a mildly enlarged, soft and yellow liver, swollen and congested kidneys and serosanguinous gastric contents. Histological sections of the kidneys revealed a mild diffuse interstitial lymphocytic infiltrate forming focal aggregates at places, accompanied with cloudy change of the tubules and focal tubular necrosis (Figure 1). The most severe lesions were seen in the lungs. They showed that majority of the alveoli and airways were filled with haemorrhage (Figure 2). Sections of the liver showed focal necrosis and a mononuclear portal inflammation while the brain revealed ischemic changes in the neurons. Levaditi's stain on the kidney sections showed numerous blackish, tiny curved rods resembling leptospira (Figure 3). Immunohistochemisty for leptospira performed on the kidney sections confirmed the diagnosis of leptospirosis (Figure 4).

Discussion

Leptospirosis, a worldwide zoonosis affecting rodents and several other mammals, is commonly transmitted to humans by contact with the excreta of the infected natural reservoirs. The disease, in humans, is characterised by multisystem involvement, protean manifestations and varying severity ranging from subclinical to fulminant, potentially fatal infection. Deaths are usually associated with severe jaundice, oliguric renal failure and a bleeding diathesis.^1,2 In the past, pulmonary manifestations were reported to be less prominent. Haemoptysis was observed in 3-25% of patients and chest pain in 10%.³ In recent years, however, epidemics of leptospirosis wherein pulmonary manifestations dominated the clinical picture have been reported from Nicaragua,⁴ the Andamans,⁵ Seychelles⁶ and Queensland,⁷ to name a few. Patients presented with an acute febrile illness and many deaths occurred with one to two days due to pulmonary haemorrhage and severe respiratory distress. Serological tests proved useful in the diagnosis and for identification of species and serotypes. Histopathological lesions seen at autopsy were massive intra-alveolar haemorrhage with or without diffuse alveolar damage, focal interstitial nephritis and mild steatosis with mononuclear portal infiltrates.⁴ The epidemic of leptospirosis that occurred following heavy monsoon floods in Mumbai in the year 2000 was also associated with prominent pulmonary involvement.

Severe pulmonary haemorrhage can occur in conditions other than leptospirosis e.g. falciparum malaria, septicaemia with disseminated intravascular coagulation, etc. Hence demonstration of organisms is essential for a specific diagnosis at autopsy. The causative organisms are delicate spirochaetes, 7- 14 mm long and 1 mm broad with one end that is often bent to form a hook. They can be demonstrated in urine by dark ground microscopy and in tissues by silver impregnation methods like the Levaditi's stain. Immunohistochemistry, however is more sensitive and specific.⁴

Leptospirosis presenting with pulmonary haemorrhage is associated with a significant mortality, however, the course can be altered by early diagnosis and prompt therapy. Many cases however go undiagnosed in the early stages because the signs and symptoms are non-specific. Leptospirosis which appears to be re-emerging as an important infectious disease should be included in the differential diagnosis when a febrile illness occurs with respiratory symptoms, especially if abnormal renal, hepatic and/or bleeding manifestations are also observed. The pathological lesions seen in leptospirosis are non-specific and special stains, immunohistochemistry as well as serological tests on post-mortem blood samples are valuable in confirming the autopsy diagnosis of leptospirosis.

References

1. Speelman P. Leptospirosis. In: Fauci AS, Braunwald E, Isselbacher KJ, Wilson JD, Martin JB, Kasper DL, et al. editors. Harrison's principles of Internal Medicine. 14th edn. New York: McGraw Hill; 1998. p. 1036-8.
2. Plank R, Dean D. Overview of the epidemiology, microbiology and pathogenesis of Leptospira spp. in humans. Microbes Infect 2000; 2:1265-76.
3. Burke BJ, Searle JF, Mattingly D. Leptospirosis presenting with profuse hemoptysis. Br Med J 1976;2:982.
4. Zaki S R, Shieh W J. Leptospirosis associated with outbreak of acute febrile illness and pulmonary haemorrhage, Nicaragua 1995. The Epidemic Working Group at Ministry of Health in Nicaragua. Lancet 1996;347:535-6.
5. Sehgal SC, Vijayachari P, Smythe L D, Norris M, Symmonds M, Dount M, et al. Lai-like leptospira from Andaman Islands. Indian J Med Res 2000;112:135-9.
6. Yersin C, Bovet P, Merien F, Clement J, Laille M, VanRaust M, et al. Pulmonary haemorrhage as a predominant cause of death in leptospirosis in Seychelles. Trans R Soc Trop Med Hyg 2000;94:71-6.
7. Simpson FG, Green KA, Hang GJ, Brookes DL. Leptospirosis associated with severe pulmonary haemorrhage in Far North Queensland. Med J Aust 1998;169:151-3.

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