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ORIGINAL ARTICLE  
Year : 2021  |  Volume : 64  |  Issue : 4  |  Page : 651-654
Acute rheumatic fever – A pathological analysis of clinically missed cases


1 Intern, Seth GS Medical College and KEM Hospital, Mumbai, Maharashtra, India
2 Department of Pathology (Cardiovascular and Thoracic Division), Seth GS Medical College, Mumbai, Maharashtra, India
3 Consultant Cardiologist, Mahatma Gandhi Mission Hospitals, Mumbai, Maharashtra, India

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Date of Submission11-Dec-2020
Date of Decision13-Feb-2021
Date of Acceptance01-Mar-2021
Date of Web Publication20-Oct-2021
 

   Abstract 


Background: Acute rheumatic fever (ARF) and its post-inflammatory sequel chronic rheumatic heart disease (RHD) are endemic in the Indian setting. Despite the updated Jones criteria, many cases of ARF remain undiagnosed or are missed. Aims: This study aims to analyze pathological profiles of such cases and their importance in context of clinical presentation and Jones criteria. Materials and Methods: A 22-year retrospective observational study of ARF was conducted in the Department of Pathology in a tertiary care institute. The cases were categorized as 1. Those fulfilling and 2. those partially or not fulfilling the Jones Criteria. Based on the autopsy findings, the lesions were classified as categorized mitral stenosis and/or regurgitation (MS ± MR) and pure mitral regurgitation (MR). Statistical Analysis: Nil. Results: In 22 years, among 697 cases of autopsied cases of RHD, there were 59 cases (8.5%) of ARF. Among them, seven cases fulfilled the Jones criteria; five of them were clinically diagnosed. The remaining 52 cases (88.1%, 34 with MS ± MR and 18 with MR) did not fulfill or partially fulfilled the Jones criteria and were not diagnosed. A total of 18 patients (30.5%) had the first attack of ARF, whereas recurrences were noted in the remaining patients (69.5%). Conclusions: The study indicates that the typical manifestations of ARF under Jones criteria may not be present, especially in cases with recurrence. Hence, a presumptive or possible diagnosis of ARF can be made with presence of minor criteria or strong clinical suspicion in such cases.

Keywords: Acute rheumatic fever, autopsy, myocarditis, rheumatic heart disease, valvular regurgitation, valvular stenosis, valvulitis

How to cite this article:
Goyal A, Vaideeswar P, Daga P, Bhargav R. Acute rheumatic fever – A pathological analysis of clinically missed cases. Indian J Pathol Microbiol 2021;64:651-4

How to cite this URL:
Goyal A, Vaideeswar P, Daga P, Bhargav R. Acute rheumatic fever – A pathological analysis of clinically missed cases. Indian J Pathol Microbiol [serial online] 2021 [cited 2021 Nov 28];64:651-4. Available from: https://www.ijpmonline.org/text.asp?2021/64/4/651/328543





   Introduction Top


Acute rheumatic fever (ARF) is a non-suppurative complication of group A beta-hemolytic streptococcal infection and represents the acute phase of rheumatic heart disease (RHD). The disease tends to affect young children and adolescents and in due course of time, leads to chronic RHD, an important cause of morbidity and mortality in Indian scenario.[1] This is not surprising since poverty, overcrowding, improper access to healthcare and under nutrition are recognized risk factors in a background of genetic predisposition.[2] The prevalence of disease burden through school-based clinical surveys is estimated to be 0.5–1.47 per 1000 children.[3] Currently, the revised Jones criteria, which now includes echocardiographic criteria and population-based risk stratifications, is said to improve the rates of clinical identification.[4] Despite the revision, it is possible that cases of ARF may remain under diagnosed. This is an autopsy analysis of cases of ARF to highlight cases, which have been missed.


   Materials and Methods Top


It is a retrospective observational study carried out at a tertiary care institute under the purview of Department of Pathology. Autopsy-confirmed cases of ARF were collected from the records preserved in the department from years 1996 to 2017. The data retrieved in all cases included the demographic data, clinical presentation, investigational profile, and autopsy findings (both gross and histopathological features). The clinical symptoms and signs were analyzed in context of revised Jones criteria[4] for diagnosis of ARF. The cases were then classified retrospectively into two categories of: 1. Those fulfilling the Jones criteria and 2. those partially/not fulfilling the Jones criteria.

All the heart specimens had been dissected by the inflow–outflow technique and weight was taken after removal of the blood clots. The atrio-ventricular and arterial valves were examined for annular dilatation, presence of leaflet/cuspal thickening and rheumatic vegetations, commissural fusion, and chordal changes. The chambers were inspected for their sizes, appearance of the endocardia, and appearance/thickness of the myocardia. Changes in the visceral pericardium were also noted. Relevant sections were taken from all chambers and valves. With clinicopathological correlation, the cases were further categorized into those with pure mitral regurgitation (MR) and those with mitral stenosis and/or MR (MS ± MR) with the presence of the first or recurrent episode of ARF.


   Results Top


In a span of 22 years, a total of 697 cases of RHD were autopsied, of which 59 were pathologically diagnosed as ARF (8.5%). Most of the patients (37, 62.7%) were females.

Cases fulfilling the Jones criteria

Seven patients (11.9%, four children and three adolescents, four females and three males) presented with characteristic features of fever, polyarthralgia, raised erythrocyte sedimentation rate/C-reactive protein (CRP), and carditis on clinical examination or imaging, thus fulfilling the Jones criteria. Five among them who were clinically diagnosed as ARF had features of MR. A thrombus attached to the supravalvular portion of the ascending aorta affected by Takayasu disease was misinterpreted as infective endocarditis of the aortic valve in the 6th patient. The 7th patient (11 years, female) had already developed MS, which indicated recurrence of the ARF. The hearts (mean weight 210 g) in all these cases displayed prominent granulomatous myocarditis with verrucuous endocarditis of the mitral and/or other valves; fibrinous pericarditis was seen in four hearts [Figure 1].
Figure 1: (a) Anterior aspect of the heart showing enlargement of all chambers. Note absence of pericardial abnormality. (b) Close up of the mitral valve showing an almost continuous row of pin-head sized vegetations. There is mild commissural fusion and thickening of the leaflets. The tendinous chords are of adequate length. (c) The left ventricular myocardium revealed multiple globose granulomatous Aschoff body in the interstitium. * indicates the central fibrinoid necrosis

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Cases partially/not fulfilling the Jones criteria

A total of 52 patients (88.1%) of total pathologically proven ARF patients were clinically either not satisfying Jones criteria or fulfilling that to some extent at best. Based on valvular lesions, they were classified and analyzed into two categories:

a. Mitral Stenosis ± Regurgitation [Table 1]: This cohort was composed of 34 patients (57.6%, 13 males and 21 females), representing recurrent ARF with an age range of 9–51 years and mean age of 24.3 years. Most of the patients presented with progressive dyspnea (27 cases, 79.4% with or without associated orthopnea or paroxysmal nocturnal dyspnea) and fever (13 cases, 38.2%). Three of the patients had sudden deaths with a past history of bronchial asthma in one of them. Remaining 31 of them had been admitted for a period of 3 h to 7 days. In 27 of these patients, a clinical diagnosis of rheumatic MS ± MR had been made with current or past interventions, valvular repair or replacements made in 10. A history of ARF and Down's syndrome was seen in one patient each. On autopsy, the hearts showed mild to moderate cardiomegaly with a mean weight of 340.4 g (110–650 g). Large numbers of Aschoff's bodies in their proliferative phases were seen in the myocardium, particularly in the left ventricle in all the cases, whereas rheumatic vegetations were identified either macroscopically or microscopically in 13 patients, especially the tricuspid valve.
Table 1: Cases partially/not fulfilling the Jones criteria - Mitral stenosis±regurgitation

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b. MR [Table 2]: A total of 18 patients (30.5%) were under this category of which 6 were males and 12 females with an age range of 5–25 years (mean age of 15.2 years). The patients were hospitalized for duration of admitted in range of 5 h to 21 days. Dyspnea (77.8%) and fever (61.1%) were the most reported complaints. Five patients had ARF recurrence and a history of ARF had been documented in three of these cases. Rheumatic MR with or without other valvular incompetence had been diagnosed clinically in 13 patients, 3 of whom had undergone replacements recently or in the past. ARF was an incidental finding in an accidental case of 62% burns. The weights of heart were in range from 160 g to 710 g (mean 354.3 g). All the heart specimens showed variable degree of cardiomegaly. Granulomatous myocarditis and verrucuous endocarditis (affecting one or more valves) was present in all the cases. Vegetations were more commonly seen on the mitral valves. Pericarditis was present in nine cases and had produced a constrictive pathology in one of them.
Table 2: Cases partially/not fulfilling the Jones criteria - mitral regurgitation

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   Discussion Top


To aid the clinical diagnosis of ARF, the five principal manifestation of the disease in the form of carditis, polyarthritis, Sydenham chorea, subcutaneous nodules, and erythema marginatum were assigned as “major” criteria. These alongside other “minor” clinical (fever and polyarthralgia) and investigational (elevated levels of CRP, raised erythrocyte sedimentation rate, and prolonged PR interval) features are assessed in combination as the Jones criteria, as outlined in 1944.[5] They have been periodically update or revised, especially with the advent of echocardiography with its utility in diagnosing sub-clinical carditis.[6] The latest revision is particularly important and relevant[4] because of the population division into high-risk and low-risk groups and the inclusion of monoarthritis/polyarthralgia and monoarthralgia as major and minor criteria, respectively, in the high-risk populations (as in India). However, the clinical diagnosis is still to be made in a patient with two major or one major and two minor criteria in a setting of prior streptococcal pharyngitis or rising titer of anti-streptococcal antibodies.[4]

In the present study spread over 22 years, we encountered 59 cases of ARF at autopsy. When the clinical presentation and pathological features were reviewed, 18 patients (30.5%) had the first attack of ARF at the time of death. Not surprisingly, 16 of them were children or adolescents, and the remaining two were young adults. The involvement in this group is well established[3],[7] and same was observed in the present study. Similar scenario can also be present in the low-risk population,[8] with involvement of adults as well.[9] In two patients (cases of Fallot's tetralogy and burns), ARF had been incidentally detected. The 16 other patients had MR. Jones criteria had been fulfilled in only six patients, with an ARF diagnosis in five of them. In the remaining ten patients, the symptoms were related with MR and/or the ensuing cardiac failure with associated fever, monoarthritis and sore throat in only four of these patients. A total of 41 of the 59 patients with well-established rheumatic valvular deformities had recurrent ARF. Pure MR was present in six patients (mean age of 16.5 years), whereas the rest of the 35 (mean age of 24.2 years) had MS of varying degrees with or without MR; the oldest patient was aged 51 years. The recurrence was noted in only patient, an 11-year-old girl with MS due to fulfilled Jones criteria. Fever (21 patients) was the main association with monoarthritis, raised CRP or elevated anti-streptolysin O (ASLO) titer in four cases. Based on our observations, we emphasize that in recurrent attacks, a presumptive or possible diagnosis of ARF can be made with the presence of minor criteria or strong clinical suspicion.[4],[6] Also with chronic valvular involvement it may not be possible to rely on echocardiography for confirming the presence of an acute episode.

ARF is usually depicted as a pancarditis, with affection of all the layers of the heart. In this study, pericarditis was noted in only 17 hearts (28.8%, constrictive pathology in one of them). In all the 18 hearts with first attack of ARF, acute valvulitis was present in the mitral and/or other valves, though acute verrucuous endocarditis was seen in 16 cases (88.9%). All four heart valves were affected in two cases. In 41 patients with ARF recurrence, only 16 hearts (39%) revealed rheumatic vegetations, which were seen to be present commonly over the tricuspid valves. In sharp contrast to the varying degrees of pericardial and acute valvular involvement, granulomatous myocarditis was present in all, leading to clinical deterioration and death in 46 patients (78%). Often when patients with chronic RHD develop exacerbations of their symptoms, it is often and rightfully attributed to progression of pulmonary hypertension (PH). The vascular changes of PH were not present in any of patients who had the initial attack, and mild to moderate PH was present in only in less than 50% of patients with MS ± MR. Also, a suspicion of infective endocarditis arises in all these patients with development of fever, though this complication was present in two patients involving native and prosthetic aortic valves.

From this analysis, we feel that there should be a high-grade of suspicion to recognize ARF (particularly its recurrent form), in patients with RHD who develop fever or exacerbations of their existing symptoms, irrespective of their ages. A thorough clinical examination and investigations required for fulfilling the major or minor criteria be conducted at the earliest so that effective treatment can be instituted.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
   References Top

1.
Watkins DA, Johnson CO, Colquhoun SM, Karthikeyan G, Beaton A, Bukhman G, et al. Global, regional, and national burden of rheumatic heart disease, 1990–2015. N Engl J Med 2017;377:713-22.  Back to cited text no. 1
    
2.
Kumar R. Rheumatic heart disease: A neglected public health priority. Indian J Public Health 2019;63:1-3.  Back to cited text no. 2
[PUBMED]  [Full text]  
3.
Arvind B, Ramakrishnan S. Rheumatic fever and rheumatic heart disease in children. Indian J Pediatr 2020;87:305-11.  Back to cited text no. 3
    
4.
Gewitz MH, Baltimore RS, Tani LY, Sable CA, Shulman ST, Carapetis J, et al. American heart association committee on rheumatic fever, endocarditis and Kawasaki disease of the council on cardiovascular disease in the young. Revision of the Jones criteria for the diagnosis of the rheumatic fever in the era of Doppler echocardiography: A scientific statement of the American heart association. Circulation 2015;131:1806-18.  Back to cited text no. 4
    
5.
Jones TD. The diagnosis of rheumatic fever. JAMA 1944;126:481-4.  Back to cited text no. 5
    
6.
Burke RJ, Chang C. Diagnostic criteria of acute rheumatic fever. Autoimmun Rev 2014;13:503-7.  Back to cited text no. 6
    
7.
Karthikeyan G, Guiltherme L. Acute rheumatic fever. Lancet 2018;392:161-74.  Back to cited text no. 7
    
8.
Fabi M, Calichhia M, Miniaci A, Balducci A, Tronconi E, Bonetti S, et al. Carditis in acute rheumatic fever in a high-income and moderate risk country. J Pediatr 2019;215:187-91.  Back to cited text no. 8
    
9.
Khan A, Sutcliffe N, Jawad ASM. An old disease re-emerging: Acute rheumatic fever. Clin Med 2018;18:400-2.  Back to cited text no. 9
    

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Correspondence Address:
Pradeep Vaideeswar
Department of Pathology (Cardiovascular and Thoracic Division), Seth GS Medical College, Mumbai, Maharashtra
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/IJPM.IJPM_1422_20

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