Description

• Acute rheumatic fever (ARF) is a recurrent inflammatory disease, possibly autoimmune in nature, that affects multiple organ systems.
• Delayed nonsuppurative sequelae of pharyngeal infection with group A streptococci
• Can cause permanent cardiac valvular disease as well as acute cardiac decompensation
• Recurrences in both adults and children are common if not prevented with prophylactic antibiotic treatment
• System(s) affected: Cardiovascular, Hematologic/Lymphatic/Immunologic, Musculoskeletal, Nervous, Skin/Exocrine

• More common in children
• In early studies, ARF developed in 3% of children with untreated group A β-hemolytic streptococcal pharyngitis (1).

Epidemiology

• ARF and rheumatic heart disease (RHD) are now largely restricted to developing countries and some poor, mainly indigenous populations of wealthy countries.
• Predominant age: Children ages 5–15 years
• Predominant sex: Male = Female; females are more prone to develop chorea.
• Worldwide, the incidence of rheumatic fever has been declining for decades due to improved living conditions, better access to health care, and the increasing use of antibiotics.
• In the US, ARF had an incidence rate of 10.2/100,000 in the 1970s and currently is <2/100,000. However, since the mid-1980s, a resurgence of cases has occurred, with multiple outbreaks likely due to immigration from high-incidence countries (1)[A].
• Currently, the incidence of ARF is highest in developing countries, exceeding 50/100,000 children in some and accounting for 95% of ARF cases worldwide (1,2)[A].

• Prevalence of RHD in the US is <0.05/1,000 population, with rare regional outbreaks.
• Worldwide, 15.6 million people have RHD. 470,000 new cases of rheumatic fever and 233,000 deaths attributable to rheumatic fever or RHD each year (1).
• The overall prevalence worldwide is rising due to advancements in medical care and longer life expectancies.

Risk Factors

Possible increased incidence with iron deficiency and low albumin concentrations (3)[C]

• Certain human leukocyte antigen (HLA) class II DR and DQ genotypes and haplotypes, particularly DR7 and DR4. Additionally, polymorphisms in the promoter region of the TNFα, IL-10, and IL-6 genes (1).
• Increased susceptibility in certain populations, including Australian Aborigines and Pacific Islanders, likely due to genetic predisposition

General Prevention

• Primary prevention: Antibiotics are effective at reducing the incidence of ARF after known or suspected group A streptococcal (GAS) pharyngitis. To achieve clinical and bacteriologic cures, treat streptococcal pharyngitis with 10 days of penicillin, an oral cephalosporin, or an oral macrolide in patients who are allergic to penicillin. Number needed to treat: 100 (4)[A].
• Secondary prevention: Long-term prophylaxis (with penicillin G or a macrolide) in selected populations

Pathophysiology

• Presents 1–4 weeks following an untreated group A β-hemolytic streptococcal pharyngitis or tonsillitis
• Molecular mimicry: Antibodies created against the M protein on cells of group A streptococcus also cross-react with various proteins in the heart and vessel walls. They subsequently attack self-cells, initiating an inflammatory cascade and causing the symptoms of rheumatic fever.

Etiology

• Preceding infection of the upper respiratory tract with group A streptococcus
• Autoimmune mechanisms