CASE

A 16 year-old male presented to the Lyndon B. Johnson Tropical Medical Center in American Samoa with a complaint of fever, chest pain, myalgias, and sore throat for three days. The patient also endorsed diffuse joint pain, particularly in his hands, knees, elbows, and shoulders, and reported intermittent, progressively worsening, pleuritic chest pain. He denied rashes, bleeding gums, or easy bruising. Mother had been giving aspirin every four hours at home without any relief.  

On exam, the patient was febrile and tachycardic. No obvious heart murmur was appreciated. He endorsed tenderness throughout his large joints, but no subcutaneous nodules were appreciated. The patient had a known history of rheumatic heart disease, but had stopped taking prophylactic antibiotics approximately one year ago. In further discussion with the patient, he reported that the monthly antibiotic injections were too painful, so he refused them.

DIAGNOSIS

 Recurrent acute rheumatic fever (ARF).

DISCUSSION

Background

ARF is a sequela of an untreated Group A Streptococcus (GAS) pharyngitis, which typically occurs two to four weeks after infection.[1] Various clinical findings can be present, including carditis, arthritis, chorea, rash (erythema marginatum), and subcutaneous nodules. If left untreated, the disease can cause gradual damage to heart valves, resulting to heart failure.

While ARF and rheumatic heart disease (RHD) have been nearly eradicated in the developed world thanks to readily availabled antibiotics, this debilitating disease is still prevalent in the developing world, particularly in settings of overcrowding and poverty. American Samoa currently has the highest prevalence of ARF/RHD in the world at 12.9%.[2] Numerous efforts have been made to increase awareness, treatment and surveillance in the country.

Diagnostic criteria

The revised Jones criteria remain the mainstay of clinically diagnosing ARF. Patients must have evidence of a recent streptococcal infection (such as positive throat cultures or elevated anti-streptolysin-O titers) plus two major criteria or one major criterion and two minor criteria [3]:

Treatment

The mainstays of treatment for ARF are antibiotics, anti-inflammatory medications, and, if indicated, heart failure management.

Step one is antibiotic treatment for GAS pharyngitis, even if throat cultures are negative. The most practical approach to treatment are long-acting intramuscular penicillin injections.[5] Repeat dosing should be given every 3-4 weeks.  Oral penicillin is also an option, but has lower rates of long-term compliance.  Patients with cardiac involvement should remain on prophylactic antibiotics for at least ten years. If patients are penicillin allergic, a sulfonamide or macrolide is a reasonable alternative. Additionally, all household contacts should receive throat cultures for GAS testing and, if positive, should receive antibiotics to prevent develop of ARF. 

Patients typically suffer from a migratory polyarthritis of their large joints, and this is treated with non-steroidal anti-inflammatory drugs (NSAIDs). High-dose aspirin has historically been the mainstay of treatment. However, other NSAIDs, such as naproxen, have also proven effective. These medications should be continued until symptoms resolve. If gastrointestinal symptoms occur with the use of NSAIDs, physicians can consider adding proton pump inhibitor. 

Regarding the acute phase of carditis, there are limited treatment options. Unfortunately, anti-inflammatory medications have not demonstrated a clinical benefit, and secondary prophylaxis with antibiotics to prevent recurrence and standard heart failure treatment remain the standard of care. Valve surgery is rarely required in the acute phase, although rupture of chordae tendineae or valve leaflets may require emergent surgery. There are no cardiac surgeons in American Samoa so these patients would have to be transferred to the mainland United States for definitive treatment.

Sydenham chorea is a less common manifestation of ARF and is typically self-limited. For those with severe symptoms interfering with daily life, dopamine receptor blocking agents, such as carbamazepine or valproic acid, are treatment options. There is also evidence of benefit with prednisone as well.[6]

CASE RESOLUTION

Our met the Jones criteria for ARF. His lab work had a positive ASO titer and he met two major criteria with carditis and joint involvement. He also met minor criteria with his fevers and arthralgias. Given the patient’s chest pain, an electrocardiogram and chest x-ray were also obtained.

The EKG demonstrated a junctional rhythm without any acute ischemic changes. The chest x-ray was also grossly unremarkable. The pediatrics team was consulted and recommended high dose aspirin (6.5 grams/day). He was also given a dose of intramuscular penicillin during his initial evaluation. They followed with the patient closely in clinic to ensure medication compliance going forward. The pediatrics team also scheduled the patient for an echocardiogram to evaluate for valvular involvement.  

TAKE-AWAYS

• RHD and ARF remain prevalent in the developing world, where people live in crowded conditions with poor sanitation.

• These diseases are particularly common in parts of the South Pacific, including American Samoa.

• Early treatment and patient education regarding importance of long term adherence to prophylactic antibiotics remain the most important factors in preventing the progression of this disease.

Author: Michael Wilk, MD recently graduated residency from Brown Emergency Medicine.

Faculty Reviewer: Alison Hayward, MD, MPH, is an assistant professor in medical education and global health in the Department of Emergency Medicine at Brown.

REFERENCES

1. Rammelkamp CH Jr, Stoltzer BL. The latent period before the onset of acute rheumatic fever. Yale J Biol Med 1961; 34:386.

2. Huang JH, et al. Echocardiographic Screening of Rheumatic Heart Disease in American Samoa. Pediatr Cardiol. 2018 Jan;39(1):38-44. doi: 10.1007/s00246-017-1724-4. Epub 2017 Sep 20.

3. Gewitz MH, Baltimore RS, Tani LY, et al. Revision of the Jones Criteria for the diagnosis of acute rheumatic fever in the era of Doppler echocardiography: a scientific statement from the American Heart Association. Circulation 2015; 131:1806.

4. Binotto MA, Guilherme L, Tanaka AC. Rheumatic fever. Images Paediatr Cardiol 2002; 11:12.

5. Webb RH, Grant C, Harnden A. Acute rheumatic fever. BMJ 2015; 351:h3443.

6. Paz JA, Silva CA, Marques-Dias MJ. Randomized double-blind study with prednisone in Sydenham's chorea. Pediatr Neurol 2006; 34:264.