Chest Discomfort in Sore Throat Patients: A Serious Under-Reported Entity Non-rheumatic perimyocarditis associated with group A streptococcal infection




Non-rheumatic streptococcal perimyocarditis (NRSP) is a relatively new and an under-reported entity in patients with group-A beta hemolytic streptococcal (GAS) pharyngitis. Most reported cases have occurred in young males, and have good prognosis. The cause and natural history is unclear, at least four different mechanisms are debated. Literature indicates an average latency of 4.6 days to the onset of chest pain following throat pain. We describe our case of NRSP in a young male patient who presented with chest pain the same day as the onset of throat pain, and we discuss our findings in the context of previously reported cases.



A 20 year old Hispanic male was admitted with chest pain, sore throat, cough, and fever of 39oC. On the day prior to hospital admission, he was seen in the emergency department with one day history of sore throat, cough, low grade fever and mild chest discomfort. A throat culture was obtained prior to antibiotic therapy and he was discharged on ibuprofen and clindamycin, due to a penicillin allergy. Later that night, he experienced worsening of his symptoms and presented again with chest pain radiating to left shoulder and arm. Treatment in the emergency department comprised intravenous clindamycin, aspirin, morphine, and ibuprofen. Physical examination revealed temperature 39oC, blood pressure 120/60 mmHg, and pulse of 110 beats per minute. Oral exam revealed pharyngeal erythema, edema and a tonsillar exudate. Heart sounds were normal. Initial laboratory findings revealed leukocytosis of 14,700/microl, serum troponin 5.17 ng/ml, creatinine kinase 500 IU/L and MB fraction 54.5 ng/ml. An electrocardiogram (ECG) revealed ST elevation in leads I, II, AVL, V1–V4. Chest radiography was normal. Echocardiography revealed severe anterior apical hypokinesis, and borderline contractility of left ventricle with ejection fraction of 52%, with no evidence of pericardial effusion. Throat culture grew group A beta hemolytic Streptococcus. Blood cultures were negative. Virus analysis was negative for Coxsackie B-virus, Epstein-Barr virus, and Human Immunodeficiency virus. He was admitted to the intensive care unit. Emergent cardiac catheterization demonstrated patent epicardial coronary arteries, and low normal LV ejection fraction and severe apical hypokinesis. It was felt that the ECG changes and positive cardiac enzymes were due to myocarditis rather than an ischemic process. Patient received intravenous clindamycin and nonsteroidal anti-inflammatory agents, and showed clinical and biochemical improvement during day 2 of hospitalization and had complete resolution of clinical symptoms by day 7.


Non-rheumatic streptococcal perimyocarditis (NRSP) is a relatively new and may be an under-reported entity in patients with group-A beta hemolytic streptococcal (GAS) pharyngitis. Most patients, as in our case, are young males and have a good prognosis. The pathophysiology of this phenomenon remains uncertain, although at least four separate mechanisms have been suggested.

The autoimmune pathogenesis of NRSP is the mechanism with the most evidence. Autoimmune responses implicated involve molecular mimicry and cross-reactivity between streptococci and the human myocytes. It remains unclear whether the host autoimmune responses cause myocardial disease or appear as a result of myocardial injury. The autoimmune response has biological effects on the heart which can modify cardiac function. Dell et al. have demonstrated cross-reactivity of human cardiac myosin epitopes with group A streptococci. id Malkiel et al. studied the T-cell dependant antibody response to dominant epitope of streptococcal polysaccharide i.e N-acetyl-glucosamine (GlcNAc), and speculated significant antigenic homology between myosin and GlcNAc. id Consecutively, the pathogenic antibody response in streptococcus induced perimyocarditis might reflect the conversion of a T-cell-independent response to GlcNAc to a T-cell-dependent cross-reactive response to GlcNAc and myosin. Cunningham et al. also identified T-cell mimicry as a potential inflammatory mechanism in the streptococcal induced perimyocadial disease. id  Although molecular mimicry between host and pathogen remains the most evidence-based sole factor involved, mimicry in combination with elevated cytokines during an infection might predispose to the development of NRSP.

A second proposed mechanism is direct involvement by bacterial component or toxin causing simultaneous tonsillitis and perimyocarditis. id Ozkaya et al. described a case of pancarditis related to direct bacterial invasion due to a new emm-type 12 allele of streptococcus pyogenes in an immunocompetent patient. id However, sporadic reports suggest that bacteria are not associated with the lesions in the heart, and the direct myocardial invasion of bacteria is improbable. id If such an event indeed took place, the organisms must have been destroyed rapidly, because no organisms were histologically identified in the myocardial lesions in fatal cases. id

Third, the release of streptococcal toxins and fragments following bactericidal antibiotic therapy is another mechanism believed to initiate perimyocardial injury. id Yet others have suggested that perimyocarditis is a hypersensitivity response to penicillin. id However, in our patient the presence of chest pain before antibiotic therapy and use of clindamycin rather than penicillin argue strongly against the validity of these hypotheses.

The literature suggests a latency of 2 to 8 days to the onset of chest pain following throat pain (average latency, 4.6 days). id  Our case is the first to show no latency period between the cardiac event and the pharyngitis. The onset of chest discomfort immediately following throat symptoms anticipate an induction of immune response, at least of an unknown order, which might trigger a cascade of inflammatory events. The findings necessitate a consideration about how exposure to streptococcal antigen and/or toxins renders a response sufficient enough to deteriorate cardiac function rapidly. Recognition of host and microbial epitopes by T cells and/or an induction of cytokine milieu might be possible explanation of the acute pathogenicity. Whether such an initial interaction is a prelude to the development of rheumatic fever remains a question of concern.

On review of literature, we did not find any female cases of NRSP (Table 1) [fig. id] . The observations suggest that there is high incidence of NRSP in males as compared to acute rheumatic fever, where the male female ratio is 1:1. The reason for this disparity is unclear, however suggests a different biological mechanism responsible for acute rheumatic fever.

Well executed clinical studies need to identify the cytokines, if involved, and establish their potential role in the pathogenesis of NRSP. As our case described, the symptoms may resolve with appropriate antibiotic therapy. However, it remains unclear whether chronic antibiotic prophylaxis would be necessary in patients who recover from NRSP, especially in those with frequent exposure to streptococcal infection.

In conclusion, the presence of a sore throat in a young male presenting with chest pain suggests an acute perimyocardial process, and should alert the clinician about the possibility of NRSP. Since this condition has good prognosis, care must be taken to distinguish these patients from other patients with myocardial ischemic disease. Further research is required to establish the pathogenesis and possible prevention of NRSP.


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