Continuing Education Activity

Acute rheumatic fever (ARF) is an abnormal immunologic response to group A Streptococcus (GAS) infections, most commonly tonsillopharyngitis. ARF affects multiple organ systems and may have cardiac, neurologic, musculoskeletal, or dermatological manifestations. While ARF most commonly occurs in children, it can affect people of any age. The recurrence rate of ARF is very high, particularly in patients with limited access to healthcare. Severe or recurrent bouts of ARF can result in significant morbidity and mortality and the development of rheumatic heart disease (RHD). The mainstay of ARF treatment includes GAS eradication therapy, management of symptoms, and secondary prophylaxis against recurrence. Prompt diagnosis and treatment of ARF are essential in preventing complications and consequences of the disease. This activity reviews the etiology, epidemiology, pathogenesis, pathophysiology, presenting symptoms and signs, complications, evaluation, and short- and long-term ARF management and highlights the interprofessional team's critical role in providing optimized care to patients with this serious condition.

Objectives:

• Correlate the pathogenesis and pathophysiology of acute rheumatic fever with common presenting clinical symptoms.
• Identify patients with acute rheumatic fever based on their clinical presentation.
• Assess and manage the complications of acute rheumatic fever.
• Develop and implement interprofessional team strategies to improve outcomes for patients with acute rheumatic fever and rheumatic heart disease.

Introduction

Acute rheumatic fever (ARF) is an immune-mediated nonsuppurative complication of group A streptococcal (GAS) pharyngitis.[1] Approximately 470,000 new cases of ARF occur annually, with a more significant disease burden in developing countries with higher rates of untreated or inadequately treated GAS infections.[2] Globally, over 275,000 deaths yearly are attributed to rheumatic heart disease (RHD).[3] The most significant contributors to the spread of GAS pharyngitis are household overcrowding, poor sanitation, and inadequate access to healthcare.[4]

The pathophysiology of ARF is characterized by an aberrant immune response to GAS infection triggered by molecular mimicry between GAS antigens and self-antigens. This immune response typically manifests 2 to 4 weeks after the initial GAS infection and may lead to the development of carditis, valvulitis, Sydenham chorea, subcutaneous nodules, erythema marginatum, and polyarthritis that is usually migratory.[5] The severity and distribution of these manifestations vary significantly between individuals making the diagnosis of ARF challenging. Early recognition of ARF using the modified Jones criteria is essential in treating acute infection and preventing complications. A major long-term consequence is RHD, which carries significant morbidity and mortality.

Etiology

ARF is an inflammatory response to a preceding GAS pharyngeal infection. GAS infections can manifest as a broad range of clinical conditions, from superficial infections such as impetigo and pharyngitis to more invasive processes, including toxic shock syndrome and necrotizing fasciitis.[6] ARF is more strongly associated with GAS pharyngitis than skin infections.[7] However, some data suggest that skin infections, particularly impetigo, may play a role for high-risk populations such as the Indigenous people of Australia.[8]

In most cases, appropriate antibiotic treatment of acute GAS infection prevents the development of ARF. Individuals with GAS infection who cannot seek medical care or have subclinical GAS infection and do not present to care are at risk for developing ARF. Environmental and socioeconomic factors, such as household overcrowding, also play a significant role in spreading GAS infections and developing ARF.

Epidemiology

There are approximately 470,000 new cases of ARF and 233,000 attributable deaths to ARF or RHD yearly.[9] Overall, the incidence and severity of ARF have declined since the 1900s, likely owing to industrialization, improved housing conditions, improvement in healthcare access, and the introduction of penicillin. Historically, an estimated 3% of patients with untreated acute GAS pharyngitis develop ARF.[10] 

High-risk patients with a history of ARF have an estimated 50% recurrence rate of ARF following untreated GAS pharyngitis.[11] Globally, the reported incidence of ARF is likely underestimated due to a lack of data, primarily from developing areas. While anyone can develop ARF, the disease is most commonly seen in children between 5 and 15 years old.[12] There is no gender predilection for ARF, but females are more likely to progress to RHD.[13] 

The populations of developing countries and Indigenous people are disproportionately affected by ARF, likely due to many environmental and socioeconomic factors, including lack of access to treatment and increased GAS transmission due to overcrowding.[14] The yearly incidence of ARF in the United States is 10/100,000 compared to an annual incidence in India of 51/100,000. The Indigenous population in Australia has one of the highest reported incidence rates, ranging from 150 to 380 cases per 100,000 children aged 5 to 14 years.[15] 

In the United States, hospitalizations secondary to ARF are more common in boys, with the highest rates occurring in 6- to 11-year-old boys of Asian and Pacific Islander descent.[16] 

The significant sequela of ARF is the development of RHD. Approximately 39 million people worldwide are estimated to be living with RHD.[17] There are currently no available reports on the incidence of ARF in Africa, where it is believed that almost 50% of all cases of RHD in children younger than 15 occur.[18] 

Pathophysiology

The pathophysiology of ARF is incompletely understood but thought to be multifactorial. Preceding GAS infection is necessary for the development of ARF. Additionally, host factors and repeated exposures to GAS contribute to the pathogenesis of ARF.

Group A Streptococcus

The emm genes of GAS encode for the M and M-like proteins. There are 5 chromosomal patterns of emm genes, labeled A-E. Evidence suggests that pharyngitis-inducing strains of GAS have the more “rheumatogenic” emm gene patterns A, B, and C.[19][20] There has been a significant decrease in the circulation of rheumatogenic strains in low-risk areas like the United States.[21] However, the complete role of bacterial strains and virulence factors in the pathogenesis of ARF is incompletely understood, and it has been shown that any strain of GAS can cause ARF.[7][22] 

Molecular Mimicry

In molecular mimicry, antibodies formed against GAS antigens crossreact with self-antigens, leading to a dysregulated immune response. There are a variety of GAS antigens implicated in molecular mimicry. The M protein moiety and N-acetyl-β-D-glucosamine (NABG) of GAS species exhibit structural similarity to myosin, leading to cardiac myositis and valvulitis.[23][24] Antibody-antigen complexes may also deposit in joints leading to the characteristic migratory polyarthritis.

Aschoff bodies are granulomatous formations found on the surface of cardiac valves in patients with RHD presumptively secondary to an interaction between T-cells and upregulated expression of vascular cell adhesion molecule-1 (VCAM-1).[25] 

In animal models, antibodies to NABG crossreact with mammalian lysoganglioside and reproduce chorea, indicating that molecular mimicry may play a role in the development of Sydenham chorea.[26] In humans, the basal ganglia are impacted in Sydenham Chorea; patients with ARF demonstrate putamen enlargement with magnetic resonance imaging.[27] 

Group A carbohydrates share epitopes with keratin, and cross-reactivity may lead to erythema marginatum.[28]

Host Susceptibility

Host susceptibility to ARF is likely polygenic.[29] Monozygotic twin studies demonstrate a greater than 40% concordance risk for ARF.[30] Human leukocyte antigen alleles and tumor necrosis factor polymorphisms play a role in genetic susceptibility to acute rheumatic fever.[31][32][33] A study conducted across 8 countries in Oceania has suggested an allele on the immunoglobulin heavy chain is associated with susceptibility to ARF.[34][32] 

Histopathology

When antibodies against GAS surface antigen bind to the surface of heart valves, they upregulate vascular cell adhesion molecule 1 (VCAM1), which allows T cells to adhere to the endocardium and form granulomatous depositions characteristic of acute rheumatic fever, termed Aschoff bodies.[32] These Aschoff bodies contain areas of active inflammation with fibrinoid necrosis, lymphocytic infiltration, plasma cells, and enlarged macrophages with condensed nuclei termed Anitschkow cells. The chromatin within the nucleus of the Anitschkow cells may appear ribbon-like and resemble a caterpillar; therefore, these cells are also called caterpillar cells.[35] Over time, valvular fibrosis, histiocytosis, and neovascularization suggest developing chronic disease and RHD.[36]

The classic histopathology of skin biopsies of erythema marginatum shows a polymorphous infiltrate of neutrophils and mononuclear cells in the papillary and upper half of the reticular dermis.[37]

Biopsies of subcutaneous nodules demonstrate increased numbers of dilated blood vessels with peripherally thickened walls, fibrinoid necrosis, and fibrosis with attachment to tendons. Histologically they resemble the lesions of rheumatoid arthritis with central fibrinoid necrosis, surrounded by histiocytes, perivascular lymphocytes, and neutrophils.[38]

History and Physical

The diagnosis of ARF is clinically based on the revised Jones criteria and typically presents within 2 to 4 weeks after an untreated GAS infection, most commonly GAS pharyngitis. A history of recurrent skin infections consistent with GAS may also be a preceding illness in specific high-risk populations. As many as one-third of patients with ARF do not recall preceding pharyngitis.[39] 

The hallmarks of GAS pharyngitis include fever, throat pain, headaches, and chills. Additionally, abdominal pain, nausea, and vomiting may be present, particularly in young children. An antecedent illness with these signs and symptoms should alert clinicians to the possibility of GAS pharyngitis.[40] The clinical manifestations of ARF vary drastically; some infections may be subclinical, and a diagnosis of ARF is not made until a patient is diagnosed with cardiac disease. Most patients with ARF display constitutional symptoms, including fevers, chills, and fatigue. Arthritis or arthralgias are usually the earliest manifestations of ARF, occurring in 60% to 80% of patients. Joint symptoms are typically migratory and characterized by erythematous, swollen, and extremely tender joints; the large joints such as the knee, ankle, or wrist are most commonly affected.

Carditis is the most serious presentation of ARF. The most common physical examination findings of carditis are tachycardia or the presence of a new murmur. Carditis occurs in 50% to 80% of patients with ARF and usually presents as pancarditis within 2 to 3 weeks involving the pericardium, epicardium, myocardium, and endocardium.[41] Carditis may also present with valvulitis, often seen on left-sided high-pressure valves. The mitral valve is affected in 50% to 60% of cases of valvulitis; mitral regurgitation is usually the earliest manifestation.[42] The physical examination of patients with mitral regurgitation frequently reveals a holosystolic murmur loudest at the apex and radiating to the left axilla. Progressive valvular damage can lead to mitral stenosis.

The aortic valve is affected in 20% of patients with valvulitis.[42] Early aortic valve damage leads to aortic regurgitation, marked by a diastolic murmur heard best at the base of the heart and increased by the patient sitting forward. Progressive damage leads to aortic stenosis. The tricuspid valve is only affected in 10% of cases of valvulitis and typically results in tricuspid regurgitation.[42] 

The transition from ARF to RHD occurs when valvular lesions evolve over the years or during multiple episodes of ARF. Cardiomyopathy and heart failure can occur, even during acute rheumatic fever, due to severe pancarditis or valvulopathy.

Dermatologic manifestations of acute rheumatic fever include subcutaneous nodules and erythema marginatum. Subcutaneous nodules occur in less than 10% of patients with ARF and are firm, painless lesions over joints, predominately on extensor surfaces. These nodules are typically associated with severe carditis. Erythema marginatum occurs in less than 6% of patients with ARF and generally is a pink or pale red annular, nonpruritic rash with raised edges and central clearing found on the trunk and limbs (see Image. Erythema Marginatum). Erythema marginatum is often described as serpiginous and fleeting, appearing on one body part, fading, and reappearing elsewhere. Erythema marginatum seems to be a more common manifestation in older children with ARF.[43] 

Sydenham chorea (SC) is a neurologic manifestation of ARF that occurs in 10% to 30% of cases. It is a late-stage neurological complication usually occurring 1 to 8 months after GAS infection. SC presents as involuntary, irregular “jerking” movements of the face, hands, or feet.[44] These choreiform movements are more extreme on one side of the body and do not occur during sleep. SC can be complicated by behavioral symptoms such as agitation, anxiety, or inappropriate laughing or crying.[45] Facial grimaces and tics are common and may be accompanied by emotional lability and characteristics of obsessive-compulsive disorder. Dysarthria and dysgraphia are also frequently noted.[46] A physical examination findings characteristic for SC is the “milkmaid's sign,” where a patient cannot maintain her grip when asked to squeeze the examiner’s fingers due to intermittent loss of muscle contraction, leading to a squeeze-and-release motion. Patients with SC often lack the traditional dermatologic and joint manifestations of ARF.

Evaluation

Revised Jones Criteria

The diagnosis of ARF is mainly clinical and considered when a GAS infection is followed by the clinical manifestations outlined in the Revised Jones Criteria. In this classification scheme, low-risk populations have an ARF incidence of ≤2 per 100,000 school-aged children, and moderate- and high-risk populations have an ARF incidence of >2 per 100,000.[45]

The presence of 2 major criteria or 1 major and 2 minor criteria is required for the diagnosis of an initial episode of ARF in any risk population. The diagnosis of a recurrent episode of ARF requires 2 major criteria, 1 major and 2 minor criteria, or 3 minor criteria (see Table 1).[45] 

A presumptive diagnosis of ARF may be made without using the Jones Criteria in patients presenting with SC or indolent carditis months after GAS infection. These cases require further evaluation with an echocardiogram.

A possible case can be defined as patients who meet the criteria for an initial infection but lack evidence of preceding GAS infection. Patients with 1 major and 1 minor criteria with evidence of a preceding GAS infection are also labeled as possible cases of ARF.[47] 

Table

Table 1. Revised Jones Criteria for Diagnosing Acute Rheumatic Fever.

Detecting group A Streptococcus

The number of laboratory tests available to diagnose GAS infection has vastly increased. Throat culture remains the gold standard, but its use is limited by its time to result. Point-of-care testing is frequently used in primary care settings. Nucleic acid amplification tests (NAAT) detect GAS and normally result in less than 1 hour. NAATs for GAS a highly sensitive and do not require backup culture testing when negative.[48][49] Rapid antigen detection tests (RADT) identify the presence of the Lancefield group A carbohydrate, provide very rapid results, and are inexpensive. The sensitivity of RADT may be less than 90%; most experts recommend backup throat culture for negative RADT results due to the low sensitivity.[50] Neither the NAAT nor the RADT allows for detecting emm types or antimicrobial susceptibility if those are the goals of obtaining a test. 

Laboratory testing to assess for a recent past GAS infection may be performed using serology. Antistreptolysin O (ASO) or antideoxyribonuclease B (ADB) antibody titers are most commonly utilized. These titers usually rise 2 to 3 weeks after a GAS infection. The interpretation of titer results is age dependent (see Table 2).[51] 

Table

Table 2. Age-dependent Upper Normal Limits for Antistreptolysin O and Antideoxyribonuclease B Antibody Titers.

Cardiac Evaluation

All patients with ARF should undergo cardiac evaluation with chest radiography, electrocardiography (ECG), and echocardiography. Chest imaging may reveal cardiomegaly and pulmonary edema. The most common ECG finding is a prolongation of the PR interval, which must be adjusted for age (see Table 3). 

Table

Table 3. Age-adjusted PR Intervals.

An echocardiogram may reveal signs of valvulopathy or heart failure. One of the keys to the successful treatment of ARF is the ability to diagnose subclinical carditis, which relies on the accessibility of echocardiography. One recent study suggested that 10.8% of patients with ARF suffer from subclinical carditis diagnosed only by echocardiography.[8] The expansion of mobile echocardiography has resulted in a vast improvement in the diagnosis of carditis and should be sought even in resource-limited settings.

Treatment / Management

The treatment of ARF is multimodal and involves GAS eradication therapy, symptomatic treatment, and prophylaxis to prevent recurrence. The initial management of ARF should occur in an inpatient hospital setting. The trend of inflammatory markers helps monitor disease progression. The normalization of inflammatory markers after completion of therapy indicates disease resolution.

Group A Streptococcus Eradication Therapy

All patients diagnosed with GAS pharyngitis should receive antibiotics to treat and attempt to eradicate GAS. Similarly, all patients diagnosed with ARF should receive a course of antibiotics even if they have a negative throat culture.[52] 

The recommended antibiotic for GAS eradication therapy is penicillin; dosage is based on the patient's weight.[50] If the patient weighs less than 27kg, penicillin V 250 mg 2 to 3 times daily for 10 days is preferred; if the patient weighs more than 27kg, 500 mg 2 to 3 times daily for 10 days is recommended. A single intramuscular dose of penicillin G benzathine 600,000 units (if below 27 kg) or 1.2 million units (if above 27 kg) may also be used for GAS eradication therapy and may be preferable, as it is the recommended therapy for patients with ARF requiring secondary antibiotic prophylaxis. Amoxicillin has a slightly broader spectrum of antimicrobial activity but some practitioners prefer it for its palatability. The amoxicillin dose is 50 mg/kg/d orally for 10 days, administered once or twice daily.

Cephalosporins are recommended in cases of documented penicillin allergy with a history of anaphylaxis.[50] The most common cephalosporins administered are cephalexin, cefuroxime, cefpodoxime, or cefdinir. Macrolides are recommended when there is history of anaphylaxis to penicillin. Common macrolides administered are azithromycin at 12 mg/kg/d for 5 days with a maximum dose of 500 mg/dose and clarithromycin at 7.5 mg/kg/dose, twice daily for 10 days with a maximum dose of 250 mg/dose. There is evidence of increasing GAS resistance to macrolides.[53] Macrolide resistance is often regional and fluctuates depending on the clone of GAS circulating through a community. Clindamycin is another alternative; some have touted it as the best at eradicating the GAS carrier state. However, clindamycin has significantly more gastrointestinal adverse effects.[54]

Symptomatic Therapy

Symptomatic therapy is geared toward managing the manifestations of ARF.

Arthritis is the earliest and most common manifestation of ARF and historically has been managed with aspirin 60 to 100 mg/kg/day in divided doses until symptom resolution. However, this dosing regimen required frequent measurement of serum salicylate levels and subsequent dose adjustments while increasing the risk of developing Reye syndrome. Newer data suggest that initially treating arthritis with nonsteroidal anti-inflammatory drugs (NSAIDs), typically naproxen 5 to 10 mg/kg every 12 hours with a maximum daily dose of 1000 mg until symptoms resolve, is equally effective.[55][56] One recent study suggests that ibuprofen may be equally effective.[57] The major adverse effect of NSAID therapy is gastrointestinal upset; patients are often prescribed a concurrent proton-pump inhibitor. Glucocorticoids are recommended if the patient has an allergy to aspirin or NSAIDs.

Carditis is the most serious complication of ARF, and GAS eradication therapy removes the infection inducing the autoimmune response against cardiac tissues. Decreasing systemic inflammation has been associated with reducing the risk of developing cardiac disease. A recent systematic review assessed various therapies for carditis and their ability to prevent further cardiac damage. In summary, neither corticosteroids nor intravenous immunoglobulin (IVIG) were determined superior to aspirin therapy for this purpose.[58] Corticosteroids may help manage patients with severe acute rheumatic heart disease, marked by significant mitral regurgitation or persistent atrioventricular block.[59] 

If a patient develops heart failure or RHD, treatment can be pharmacological or surgical, depending on the severity of the cardiac disease. Pharmacotherapy options recommended for managing heart failure include fluid and salt restriction, angiotensin-converting enzyme (ACE) inhibitors, and diuretics.[42] All patients with ARF should be evaluated and followed by a cardiologist, even if carditis is not initially present, and undergo periodic evaluation to monitor for potential progression to RHD. 

Subcutaneous nodules and erythema marginatum associated with ARF are commonly self-limited.

Sydenham chorea (SC) is a late-stage finding and is generally self-limited. SC is treated with rest and avoidance of overstimulation. Immunomodulating agents have been studied as a treatment for SC and appear to have a positive impact. Studies suggest that corticosteroids will improve symptoms in patients suffering from SC. The most common treatment regimen is intravenous methylprednisolone, followed by oral prednisone.[60][61][62] Some practitioners advocate for treatment with prednisone alone.[63][64][65][66] Others have observed that patients demonstrate clinical improvement after receiving IVIG or plasmapheresis therapy.[67][68][69][60]][70]

Pharmacotherapy is recommended for SC which is negatively impacting activities of daily living. Options include carbamazepine, pimozide, haloperidol, and valproic acid for refractory cases. Haloperidol has shown efficacy, but its significant adverse effects limit its use in children.[71][72] Carbamazepine and valproic acid are effective against the symptoms of SC and have been used in children with neurologic diseases for many years.[73][74] One case report suggests that pimozide may be effective with minimal adverse effects.[75]

Secondary Antibiotic Prophylaxis

Patients with a history of ARF are at increased risk for disease recurrence and worsening RHD and should receive secondary antibiotic prophylaxis against GAS infections. Patients with SC as the only presenting symptom of ARF should also initiate secondary antibiotic prophylaxis.

Antibiotic prophylaxis typically involves the administration of intramuscular penicillin G benzathine every 28 days. In populations with a higher incidence of ARF, injections should be administered every 21 days. Oral penicillin V twice daily may be used prophylactically but is associated with decreased adherence and increased recurrence.[76] However, penicillin V is the recommended prophylactic therapy in patients with severe, symptomatic valvular disease with evidence of significant heart failure, as vasovagal episodes associated with intramuscular injections have been associated with an increased risk of sudden death. In patients with penicillin allergies, macrolides and sulfadiazines can be used. All patients with a history of penicillin allergy should undergo evaluation by an allergist to determine if they can be cleared for penicillin therapy. In cases of breakthrough GAS pharyngitis, clindamycin can be used for the acute episode before restarting penicillin prophylaxis.

The duration of secondary prophylactic therapy may vary based on evidence of carditis. Patients with echocardiographic evidence of carditis without residual valvulopathy should continue prophylactic therapy for 10 years or until age 21. Patients with evidence of residual valvulopathy should continue prophylactic therapy for 10 years or until age 40. If there is no echocardiographic evidence of carditis, prophylaxis should continue for 5 years or until the patient reaches age 21. In all cases, prophylactic therapy should be continued until the latest age criteria are met (see Table 4).[52] 

Table

Table 4. Secondary Antibiotic Prophylaxis of Acute Rheumatic Fever.

Differential Diagnosis

Patients with ARF may present with one or more clinical symptoms. The presentation of ARF varies widely. The differential diagnosis of ARF is broad and will be dictated by the presenting symptomatology. Diagnoses that may be considered include:

• Polyarthritis:

  • Lyme disease
  • Poststreptococcal reactive arthritis
  • Septic arthritis
  • Drug reactions and serum sickness
  • Postinfectious reactive arthritis 
• Carditis:

  • Endocarditis
  • Viral myocarditis
• Sydenham Chorea:

  • Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS)
  • Tardive dyskinesia
  • Tourette syndrome
• Dermatologic manifestations:

  • Urticaria
  • Scarlet fever
  • Kawasaki disease
  • Erythema multiforme
  • Erythema migrans (Lyme disease)
  • Viral exanthem
• Systemic Illnesses

  • Juvenile idiopathic arthritis
  • Kawasaki disease
  • Systemic lupus erythematosus

Prognosis

The usual course of ARF is about 3 months, and recurrence rates approximate 65%.[77] Recurrence increases the risk of progression to RHD and heart failure. Risk factors contributing to recurrence include poor adherence to prophylaxis, shorter intervals between episodes of ARF, younger age, and the presence of carditis.[78]

Cardiac involvement is the most critical prognosticating factor in ARF. Patients with carditis are at the highest risk for developing RHD, the most common cause of morbidity and mortality in patients with ARF. The long-term prognosis of ARF has significantly improved over the last century in developed areas with enhanced therapy for GAS eradication, long-term secondary prophylaxis, and improvement in living conditions. Despite this, it is very common for patients in resource-poor areas to present with late-stage RHD. Valve replacement or valvuloplasty is indicated in cases of severe rheumatic valvular disease.

A study conducted on Australian patients with cardiac disease during their ARF episode showed that 50% of patients with severe RHD underwent valvular surgery within 2 years and experienced a 10% mortality rate. Among patients with minimal carditis, 64% had mild cardiac disease even after 10 years of developing ARF. Of these patients, 11.4% progressed to clinically severe RHD, and half needed surgery.[79] 

A systematic review recently summarized the outcomes of mitral valvuloplasty versus mitral valve replacement. Patients who underwent valve repair were noted to have lower short- and long-term mortality but often required additional procedures. Surgical repair is preferred for older patients, but concomitant aortic valve disease favors mitral valve replacement.[80] 

Sydenham chorea (SC) typically will resolve in about 12-15 weeks. Persistent SC does occur, but the mechanism is unclear. Some experts suspect damage to the basal ganglia accounts for this phenomenon.[81] Additionally, psychiatric symptoms may be more prevalent in patients who have suffered from SC.[82]

Complications

The most common complicating sequela of ARF is RHD, which occurs 10 to 20 years after the original illness and is due to valvular damage by severe or recurrent bouts of ARF. RHD is the most common cause of acquired valvular pathology worldwide. RHD can lead to heart failure, pulmonary hypertension, dysrhythmias, embolic strokes, and sudden cardiac death.[83]

Another complication of ARF is Jaccuod arthropathy, a chronic, benign arthropathy that may result in joint deformities due to repeated bouts of arthritis caused by ARF.[84] The arthritic changes of Jaccoud arthropathy appear similar to the joint deformities seen with rheumatoid arthritis and include thumb subluxation, ulnar deviation, hallux valgus, and swan neck and boutonniere deformities of the fingers. However, unlike in rheumatoid arthritis, patients with Jaccoud arthropathy do not have bony erosions, and the deformations can be manipulated into a normal anatomic position. 

SC may rarely lead to persistent symptoms and has been related to increased psychiatric symptoms in some patients.

Consultations

Care for patients with ARF should be carried out in consultation with an infectious disease specialist and a cardiologist. As part of the diagnostic criteria, it will be necessary to obtain echocardiography to look for evidence of carditis. If patients develop carditis with severe valvulopathy with signs of heart failure, a cardiothoracic surgeon should be consulted to consider valvuloplasty. In patients with SC, consultation with a neurologist may be necessary. In patients with persistent arthralgias and arthritis, consultation with a rheumatologist may help design a long-term management plan.

Deterrence and Patient Education

ARF and the subsequent development of RHD are significant causes of morbidity and mortality, especially in developing countries. Deterrence involves strategies to avoid GAS pharyngitis, early detection and treatment of GAS pharyngitis, and prophylaxis against recurrent ARF. Patient education is one of the cornerstones of successful lifelong management of ARF. Patients should be informed about the consequences of their diagnosis of ARF and the importance of adherence to prophylactic antibiotic therapy. Caregivers should also be educated about the signs of GAS pharyngitis and early manifestations of acute rheumatic fever. Household and school-aged contacts are the most likely sources of GAS exposure in people with a history of ARF. 

Enhancing Healthcare Team Outcomes

The presentation and severity of ARF varies significantly. Recurrence is frequent and may be challenging to manage. Patients with ARF benefit from a multidisciplinary, interprofessional team approach. 

Primary care practitioners and urgent or emergency care clinicians are frequently the first medical contacts of patients with ARF. Recognition of the early clinical symptoms and signs is imperative to improve outcomes for patients with ARF. Prompt initiation of pharmacotherapy and early cardiac assessment is essential when evaluating and treating patients with ARF. 

If the patient evaluation reveals signs of carditis or RHD, cardiologists and cardiothoracic surgeons should primarily manage the symptoms of heart failure and valvulopathies. Consultation with an infectious disease specialist is crucial to help guide the initial treatment and secondary prophylactic therapy of ARF. A statement by the American Heart Association and endorsed by the American Academy of Pediatrics confirms that penicillin G is the most studied pharmacotherapy in the prevention of the recurrence of acute rheumatic fever, and continuous prophylaxis is the most strongly recommended intervention for those with a history of acute rheumatic fever.[52] 

All clinicians caring for patients with ARF are responsible for educating patients on the importance of adherence to pharmacotherapy and secondary antibiotic prophylaxis.

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Disclosure: MD Sadakat Chowdhury declares no relevant financial relationships with ineligible companies.

Disclosure: Christian Koziatek declares no relevant financial relationships with ineligible companies.

Disclosure: Michael Rajnik declares no relevant financial relationships with ineligible companies.