|Year : 2019 | Volume
| Issue : 3 | Page : 217-220
Leptospirosis: A Diagnostic Challenge at Autopsy: Report of Two Cases
Sharada R Rane, Varsha Bhatia
Department of Pathology, BJGMC, Pune, Maharashtra, India
|Date of Submission||02-Aug-2019|
|Date of Decision||03-Sep-2019|
|Date of Acceptance||30-Sep-2019|
|Date of Web Publication||20-Dec-2019|
Dr. Varsha Bhatia
Department of Pathology, BJGMC, Pune, Maharashtra
Source of Support: None, Conflict of Interest: None
Leptospirosis is an important sporadic zoonotic disease. This disease is caused by the spirochete leptospira icterohemorrhagica. In India, leptospirosis has always remained a major health concern, particularly during monsoons. This disease mainly affects vital organs such as the lung, kidney, and heart. Acute respiratory distress syndrome and acute renal failure mainly contribute to the mortality in patients, but cardiac involvement leading to death still remains an underestimated critical clinical factor. We report here two autopsy cases and highlight histopathological changes in heart which helped us in diagnosing in correlation with other organ findings the final cause of death as leptospirosis.
Keywords: Coronary artery endotheliitis, heart, leptospirosis
|How to cite this article:|
Rane SR, Bhatia V. Leptospirosis: A Diagnostic Challenge at Autopsy: Report of Two Cases. J Pract Cardiovasc Sci 2019;5:217-20
|How to cite this URL:|
Rane SR, Bhatia V. Leptospirosis: A Diagnostic Challenge at Autopsy: Report of Two Cases. J Pract Cardiovasc Sci [serial online] 2019 [cited 2020 Jul 16];5:217-20. Available from: http://www.j-pcs.org/text.asp?2019/5/3/217/273741
| Introduction|| |
Leptospirosis is an important zoonotic disease. It is known to occur in India for over a century. It is a major health concern, particularly during monsoons, but its accurate prevalence is still lacking worldwide as well as in India., Leptospirosis mainly presents with fever, jaundice, azotemia, anemia, and altered consciousness. But with sudden death of patient with minimal clinical history and laboratory diagnosis, it becomes extremely difficult to diagnose such cases. At postmortem, careful evaluation of histopathological changes in major organs such as the kidney, lungs, and heart becomes extremely useful in diagnosing this dreadful disease. We report here two cases showing unusual but striking histopathological findings in heart prompting us to reevaluate histopathological changes in the kidney and lungs leading to the diagnosis of leptospirosis at autopsy.
| Case Report|| |
A 26-year-old young male resident of Maharashtra, India, presented with fever and chills from the past 2 days and on admission died within 1 h. No other relevant information regarding his past illness was available.
A 32-year-old young adult male resident of Maharashtra, India, presented with the past history of jaundice and died within few hours of hospital admission. No other relevant clinical history was available.
Both the above patients were admitted to the hospital during monsoon season.
Complete medicolegal autopsy was performed in both the above cases which showed similar findings.
Both males were thin built.
The weight of the complete heart was 250 g. The pericardial surface was unremarkable. On cutting open, the left ventricular thickness was 1.5 cm. All coronary vessels were patent. All valves, chambers, chordae tendineae, and papillary muscles were unremarkable. There was no evidence of atherosclerosis or infarction on gross examination. Microscopically, sections from the heart revealed mixed inflammatory infiltrate in the interstitium of myocardium suggesting features of interstitial myocarditis [Figure 1]a. The lumen of all coronary arteries were patent, but right coronary artery showed marked endothelial proliferation with mixed inflammatory infiltrate adherent to endothelium suggestive of coronary artery endotheliitis [Figure 1]b and [Figure 1]c. Grossly, the lungs were firm in consistency and cut surface was hemorrhagic. Sections from the lung showed massive pulmonary hemorrhage [Figure 2]. Grossly external and cut surface of kidney was unremarkable but on microscopic examination kidney showed diffuse polymorphonuclear infiltrate in the interstitium suggestive of interstitial nephritis [Figure 3]. Grossly, the borders of liver were sharp and unremarkable external and cut surface. Sections from the liver showed mild portal triaditis.
|Figure 1: (a) Microphotograph of heart showing interstitial myocarditis (H and E, ×20). (b) Microphotograph shows coronary artery with patent lumen (H and E, ×40). (c) Endothelial cell proliferation with adherent mixed inflammatory cells features of coronary artery endotheliitis (H and E, ×20).|
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|Figure 2: Microphotograph of lung showing diffuse pulmonary hemorrhage (H and E, ×20).|
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|Figure 3: Microphotograph of kidney showing diffuse interstitial nephritis (H and E, ×20).|
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Based on these histomorphological findings, the possible diagnosis of infective etiology was suspected mainly leptospirosis.
For confirmation of diagnosis, tissue blocks were sent to the Centers for Disease Control and Prevention (CDC), Atlanta, USA, for immunohistochemistry (IHC) markers. The IHC results were positive for leptospira on kidney sections. It showed fragmented leptospira and granular form of bacterial antigens [Figure 4].
|Figure 4: Microphotograph of immunohistochemistry on kidney positive for leptospira (immunohistochemistry, ×60).|
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After the correlation of gross, microscopic features and IHC findings, final cause of death was given as leptospirosis [Table 1].
| Discussion|| |
Leptospirosis is acute febrile iilness that affects humans or animals. Its incidence is mainly high in the tropical developing countries. The rainy season and floods are the major source of outbreak of this disease. It is also found in rural and urban areas and linked to some occupational activities. Leptospirosis targets younger population and on an average 5%–15% of them develops severe manifestation of this disease known as Weil's disease. Our cases were also young males.
Leptospirosis presents in an epidemic proportion when there is natural calamity like floods. In such circumstances, carrier state exists in animal population causing disease transmission and leading to sporadic outbreaks as seen in India. It is endemic in Kerala, Tamil Nadu, Gujarat, Karnataka, Maharashtra, and Andaman island. Leptospirosis occurring as sporadic disease usually presents with acute febrile illness with varying degrees of jaundice and renal dysfunction. Such cases are usually diagnosed based on clinical criteria to distinguish it from other febrile illness; however, in our cases, patients with acute febrile illness and short duration of hospital stay with immediate death extensive postmortem examination is the only means to suspect or diagnose this frightful disease.
In literature, majority are clinically based studies diagnosing and confirming leptospirosis on serology.,, Only in the past few years, studies are reported which have taken postmortem examination as useful diagnostic tool to confirm this disease. At postmortem examination, the striking gross and microscopic features are mainly seen in the organs such as the lungs, kidney, and heart. These changes have been reported by Salkade et al. in their largest study of autopsy finding in leptospirosis.
In our cases, we initially observed changes in microscopic features of the heart. There was striking coronary artery endotheliitis and focal interstitial myocarditis with no significant changes in gross findings of heart. The types of vasculitis of blood vessels of the heart are Buerger's disease, Churg–Strauss syndrome, and Takayasu's arteritis, and causes can be infections such as Hepatitis B and C, drugs, and autoimmune disorders. But with limited clinical history of acute febrile illness and past history of jaundice in young patients with no evidence of cardiac involvement prompted us to go through literature search and we encountered leptospirosis as one of the infectious causes of involvement of heart showing such salient microscopic features and thus excluding other causes. There are only few case studies reported in literature describing cardiac involvement of heart in this disease.,
Leptospira enters human body through damaged skin or mucous membranes. The mechanism of injury is unclear but may include immune mechanism or toxin production. Leptospiral polysaccharides resist the innate immune defenses like complement and proliferates in blood before spreading to other organs. It causes systemic vasculitis which facilitates transndothelial migration of inflammatory cells leading to endotheliitis which is seen as coronary vessel endotheliitis in the heart.
Furthermore, extensive microscopic search of lung and kidney showed diffuse pulmonary hemorrhage and diffuse interstitial nephritis, respectively. After correlation, we suspected the cause of death in these cases was leptospirosis.
To conclusively prove it, we sought the help of IHC on tissue sections which was sent to CDC, Atlanta, and was positive for leptospirosis on kidney sections. To the best of our knowledge, very few reports have taken help of IHC to demonstrate antigen on postmortem tissue sections when there is lack of serological backup., The technique of IHC needs to be explored further and should be used routinely for accurate diagnosis of leptospirosis at autopsy and also sensitivity and specificity of IHC can be determined. However, there are limitations of IHC use because of technical and financial constraints.
Thus, the cause of death in these cases was leptospirosis after correlating characteristic microscopic features in the heart, lung, and kidney and the help of IHC on kidney sections at postmortem examination.
| Conclusion|| |
At autopsy, leptospirosis seems to be infective systemic vasculitis. There is definitive cardiac involvement in leptospirosis, although patients are relatively asymptomatic at clinical examination. This leads to considerable morbidity and mortality in such cases apart from pulmonary hemorrhagic syndrome and acute renal failure. Thus, we would like to highlight through these reports that coronary artery endotheliitis should be taken as diagnostic feature of leptospirosis as other systemic organ changes could be nonspecific inflammation. Thus findings of coronary artery endotheliitis and myocarditis should lead to suspicion of leptospirosis and IHC will be helpful for confirmation in such cases. Careful evaluation of heart findings at autopsy should be done in association with lung and kidney changes to arrive at definitive cause of death and to minimize the error in missing such cases.
Since this study is on postmortem specimen no ethical clearance needed.
We are thankful to the Centers for Disease Control and Prevention, Atlanta (Dr Sherif Zaki, Sheih, Wun-Ju Pathologist/Tina Benoit epidemiologist), for having helped us out with IHC study in our cases.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Rupani AB, Shah VB, Deshpande JR. Original article, renal changes in leptospirosis: An autopsy study. Bombay Hosp J 2007;49:278-84.
Salkade HP, Divate S, Deshpande JR, Kawishwar V, Chaturvedi R, Kandalkar BM, et al.
Astudy of sutopsy findings in 62 cases of leptospirosis in a metropolitan city in India. J Postgrad Med 2005;51:169-73.
] [Full text]
de Campos F, Simoes A. Fulminant Leptospirosis: an autopsy case. Autops Case Rep 2011;1:1-3.
Report of the Brainstorming Meeting on Leptospirosis Prevention and Control, Joint Publication of the Office of WHO Representative to India. New Delhi and Regional Medical Research Centre (ICMR), WHO Collaborating Centre for Diagnosis, Research, Reference and Training in Leptospirosis. Mumbai; 2006.
Sanford JP. Leptospirosis In: Isseibacher KJ, Braunwald E, Wilson JD, Martin JB, Fauci AS, Kasper DL, editors. Harrison's Principles of Internal Medicine. 13th
ed. New York: McGraw Hill; 1994. p. 740-3.
Ko AI, Galvão Reis M, Ribeiro Dourado CM, Johnson WD Jr., Riley LW. Urban epidemic of severe leptospirosis in Brazil. Salvador leptospirosis study group. Lancet 1999;354:820-5.
Yersin C, Bovet P, Mérien F, Wong T, Panowsky J, Perolat P. Human leptospirosis in the seychelles (Indian ocean): A population-based study. Am J Trop Med Hyg 1998;59:933-40.
Park SK, Lee SH, Rhee YK, Kang SK, Kim KJ, Kim MC, et al.
Leptospirosis in chonbuk province of Korea in 1987: A study of 93 patients. Am J Trop Med Hyg 1989;41:345-51.
Chakurkar G, Vaideeswar P, Pandit SP, Divate SA. Cardiovascular lesions in leptospirosis: An autopsy study. J Infect 2008;56:197-203.
Shah K, Amonkar GP, Kamat RN, Deshpande JR. Cardiac findings in leptospirosis. J Clin Pathol 2010;63:119-23.
Werts C, Tapping RI, Mathison JC, Chuang TH, Kravchenko V, Saint Girons I, et al.
Leptospiral lipopolysaccharide activates cells through a TLR2-dependent mechanism. Nat Immunol 2001;2:346-52.
Nicodemo AC, Duarte MI, Alves VA, Takakura CF, Santos RT, Nicodemo EL, et al.
Lung lesions in human leptospirosis: Microscopic, immunohistochemical, and ultrastructural features related to thrombocytopenia. Am J Trop Med Hyg 1997;56:181-7.
[Figure 1], [Figure 2], [Figure 3], [Figure 4]