Antibodies to streptococci can occasionally “cross-react” against host tissue, causing a febrile illness known as acute rheumatic fever (ARF) with the potential to damage end-organs, leaving them vulnerable. Because it is a relatively infrequent complication of acute streptococcal infection, whether of the throat or skin or elsewhere, Rheumatic fever not infrequently escapes clinical recognition and the person carries on with their lives unknowingly at risk of serious conditions such as bacterial endocarditis and renal failure. The pathogenesis of rheumatic heart disease (RHD) involves molecular mimicry and genetic predisposition that lead to autoimmune reactions from antibodies produced against Group A β-hemolytic streptococci (GAS). RHD, the long-term cardiac damage caused by either a single severe episode or multiple recurrent episodes of ARF, is a significant worldwide cause of morbidity and mortality, particularly in resource-poor settings. Improved living conditions and widespread treatment of superficial S. pyogenes infections have caused these diseases to become comparatively rare in developed areas. [1]
It is behooved upon clinicians working in areas of endemicity and native populations in rural and remote regions or those in crowded metropolitan settings to remain alert to the potential for rheumatic fever in their patients, not least of which because it can often present quite subtly with no more than some arthralgia. The key to diagnose is an index of suspicion to a preceding strep infection and to the manifestations of acute rheumatic fever. Rheumatic fever usually occurs about two to four weeks after a strep throat infection, and can be so mild as to escape detection. According to modified Jones criteria, the diagnosis of rheumatic fever is made where two major criteria, or one major criterion and two minor criteria, are present along with evidence of streptococcal infection: elevated or rising antistreptolysin O titre or positive strep culture or nucleic-acid amplification (NAA).
In Australia, ARF predominantly affects Aboriginal and Torres Strait Islander children aged 5–14 years living in regional and remote areas of central and north Australia, where it has an estimated incidence of 250–350 per 100 000.[2]
The hallmarks of a rheumatic fever are:
- carditis, manifesting as chest pain, fatigue or a new heart murmur
- poly arthritis or polyarthralgia (occasionally an aseptic mono arthritis), most often the ankles, knees, elbows or wrists.
- erythema marginatum and subcutaneous nodules
- Sydenham’s chorea: acute involuntary movements with psychosis (may commence more than 4 weeks after antecedent strep infection)
- fever: BT 38oC or higher
Clinical suspicion raised by any such symptoms and supported by a raised ESR or CRP should prompt evaluation and management for a rheumatic fever to prevent its pathological sequelae. Patients should be immediately referred for specialist assessment, inclusive of echocardiography, and treatment, usually requiring hospitalisation for eradication of streptococcus species and management of symptoms and any complications.
- penicillin antibiotic
- NSAID: aspirin starting at 50–60 mg/kg/day in 4 divided doses, then tapered and continued until 1-2 weeks after symptom resolution
- naproxen 10–20 mg/kg/day orally, in two divided doses, appears equally efficacious and associated with fewer side effects than aspirin[3]
- carditis management – bed rest, diuretics (frusemide, spironolactone), ACE-i, nitrates, digoxin, prednisone
- chorea management – carbamazepine (alternatively, sodium valproate or leviteracetam) risperidone, prednisone
Benzathine penicillin G 900 mg (child 3–6 kg: 225 mg, 6–10 kg: 337.5 mg, 10–15 kg: 450 mg, 15–20 kg:
675 mg) given intramuscularly as a single dose*. If penicillin sensitive, give azithromycin 500 mg (child: 12 mg/kg up to 500 mg) orally daily for 5 days.[3]
Secondary prophylaxis includes a protracted course of, preferably intramuscular, penicillin administration. To avoid recurrences of acute rheumatic fever and the development of rheumatic heart disease, future group A streptococcal infections need to be avoided using antibiotic prophylaxis with benzathine penicillin G (Table 2). Oral penicillin is strongly discouraged and is known to be associated with higher rates of acute rheumatic fever recurrence. Benzathine penicillin G 900 mg (child < 20 kg: 450 mg)* intramuscularly as a single dose once every 21 or 28 days If immediate penicillin hypersensitivity, use erythromycin 250 mg (child: 10 mg/kg up to 250 mg) orally 12-hourly. The required duration of secondary prevention for those with mild or no rheumatic heart disease is for a minimum of 10 years or until age 21 (whichever comes later), until age 35 for those with moderate heart disease, and until age 40 or longer for those with severe heart disease. [3] Needless to say, ensuring adherence to such prophylaxis is a significant challenge.
The clinical onset of acute rheumatic fever is 1–4 weeks after GABS infection, making the diagnosis more challenging. Nonetheless, antibiotic eradication therapy is still recommended. Well documented following GABS throat infection, there is circumstantial evidence implicating skin infection with group A streptococci in the pathogenesis of acute rheumatic fever in Australian and New-Zealand indigenous communities, In rare instances of true penicillin allergy, azithromycin (previously erythromycin) is now recommended treatment, albeit with a small but real rate of macrolide resistance in GABS isolates.[3]
References
- Sika-Paotonu D, Beaton A, Raghu A, et al. “Acute Rheumatic Fever and Rheumatic Heart Disease.” 2017 Mar 10 [Updated 2017 Apr 3]. In: Ferretti JJ, Stevens DL, Fischetti VA, editors. Streptococcus pyogenes : Basic Biology to Clinical Manifestations [Internet]. Oklahoma City (OK): University of Oklahoma Health Sciences Center; 2016-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK425394/.
- Smith, Michael T., Zurynski, Yvonne; Lester-Smith, David; Elliot, Elizabeth and Carapetis, Jonathan. “Rheumatic fever: Identification, management and secondary prevention.” Aus Fam Phys 41(1/2); 2012.
- Ralph AP, Noonan S, Boardman C, Halkon C, Currie BJ. “Prescribing for people with acute rheumatic fever.” Aust Prescr 2017;40:70–5. https://doi.org/10.18773/austprescr.2017.011.
