15.24C: Rheumatic Fever

Rheumatic fever is an inflammatory disease that can develop as a complication of inadequately treated strep throat.

Learning Objectives

• Outline the effect of infection by Steptococcus pyogenes on the immune system

Key Points

• Rheumatic fever is a condition that is a complication of untreated strep throat. Strep throat is caused by a group A streptococcal infection found in the throat.
• When the body senses the strep infection, it sends antibodies to fight it and sometimes these antibodies attack the tissues of your joints or heart instead. This is known as anitbody cross-reactivity which leads to rheumatic fever.
• Symptoms of rheumatic fever occur several weeks after initial throat problems have disappeared; and include chest pain, fever, heart problems, joint pain, nosebleeds, and skin rash.
• Rheumatic fever is treated using a combination of antibiotics and anti-inflammatory medications.

Key Terms

• rheumatism: Any disorder of the muscles, tendons, joints, bones, nerves, characterized by pain, discomfort and disability.
• Streptococcus: A spherical, gram-positive bacterium of the genus Streptococcus. Although commonly found benignly in the human mouth and gut, and though many species are non-pathogenic, other species can cause diseases including strep throat and more serious conditions.

Rheumatic fever is an inflammatory disease that occurs following a Streptococcus pyogenes infection, such as streptococcal pharyngitis (strep throat) or scarlet fever, that affects the peri-arteriolar connective tissue. Believed to be caused by antibody cross-reactivity that can involve the heart, joints, skin, and brain; the illness typically develops two to three weeks after a streptococcal infection.

Figure: Streptococcus pyogenes bacteria: Photomicrograph of Streptococcus pyogenes bacteria, 900x Mag. A pus specimen, viewed using Pappenheim’s stain. Last century, infections by S. pyogenes claimed many lives especially since the organism was the most important cause of puerperal fever and scarlet fever.

Acute rheumatic fever commonly appears in children between the ages of six and 15, with only 20% of first-time attacks occurring in adults. The illness is so named because of its similarity in presentation to rheumatism.

This cross-reactivity is a Type II hypersensitivity reaction and is termed molecular mimicry. During a Streptococcus infection, mature antigen -presenting cells, such as B cells, present the bacterial antigen to CD4-T cells which differentiate into helper T₂cells. In turn, Helper T₂ cells activate the B cells to become plasma cells and induce the production of antibodies against the cell wall of Streptococcus. However the antibodies may also react against the myocardium and joints, producing the symptoms of rheumatic fever.

Diagnosis of rheumatic fever can be made when two of the major criteria, or one major plus two minor criteria, are present along with evidence of streptococcal infection.

The major criteria for diagnosis include:

• Arthritis in several large joints (polyarthritis)
• Heart inflammation (carditis)
• Nodules under the skin (subcutaneous skin nodules)
• Rapid, jerky movements (chorea, Sydenham chorea)
• Skin rash (erythema marginatum)

Minor Criteria:

• Fever of 38.2–38.9 °C (101–102 F)
• Arthralgia: Joint pain without swelling (Cannot be included if polyarthritis is present as a major symptom)
• Raised erythrocyte sedimentation rate or C reactive protein
• Leukocytosis
• ECG showing features of heart block, such as a prolonged PR interval (Cannot be included if carditis is present as a major symptom)
• Previous episode of rheumatic fever or inactive heart disease.

Acute rheumatic fever is treated with antibiotics and anti-inflammatory medications such as aspirin and corticosteroids.