Rheumatic fever

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The incidence of acute rheumatic fever and the prevalence of rheumatic heart disease had declined for several decades in the United States. [1-3] Recently, however, the incidence of acute rheumatic fever has jumped, with outbreaks reported in many areas of the country. [4-11] The disease is also common among certain ethnic groups in western countries in which crowded living conditions and poverty prevail. [12,13]

The resurgence of acute rheumatic fever is occurring at a time when many physicians may be unfamiliar with its protean manifestations. [3,14,15] In addition, changes have recently been suggested in the diagnostic criteria for acute rheumatic fever, and there is controversy about the dose intervals for penicillin prophylaxis.

Diagnosis

Acute rheumatic fever is the most serious nonsuppurative sequela of group A streptococcus (Streptococcus pyogenes) infection. The onset is usually insidious, with fever, malaise and weight loss. The illness gradually worsens, and the patient finally presents to the physician with various signs and symptoms. A history of a sore throat within the preceding three months has been found in as few as 20 percent of children; it is rarely mentioned by the patient or the family unless they are specifically questioned about it.

In 1944, Jones proposed guidelines to aid in the diagnosis of acute rheumatic fever. Those guidelines have evolved into the revised Jones criteria [16] currently in use. Recent additions to these criteria have been proposed by the World Health Organization. [17] The revised criteria and the WHO additions are outlined in Table 1.

Two major criteria or one major and two minor criteria are required to make the diagnosis of acute rheumatic fever, according to the revised Jones criteria. The frequency of presenting manifestations is shown in Table 2. Most patients with acute rheumatic fever have two or more major manifestations; the combination of carditis and arthritis is the most frequent.

Major Criteria

CARDITIS

Carditis is more common now than it was 30 years ago. [18] The prevalence of cardiac involvement decreases with increasing age of the patient at the tie of the first attack of acute rheumatic fever. [19] Carditis is defined as a new or changed murmur (especially murmor of the mitral valve or of aortic incompetence), a pericardial friction rub or effusion, and a new or worsening cardiac enlargement with or without congestive heart failure.

Knowledge of a previous cardiac murmur is helpful. In the absence of a history of preexistent murmur, several auscultatory findings point toward acute carditis: an apical systolic murmur greater than grade 3/6 and lasting at least one-half of systole; any apical diastolic murmur; and muffled, distant heart sounds and the presence f a distolic third heart sound.

ARTHRITIS

The arthritis of acute rheumatic fever is often polyarticular and migratory, commonly involving the larger joints (knees, ankles, elbows and wrists). The affected joint is exquisitely tender, red, hot and swollen. Arthrocentesis yields a clear serous fluid high in protein and celss.

CHOREA

Sydenham's chorea is the most benign of the signs associated with acute rheumatic fever, usually indicating a more favorable prognosis. Concomitant carditis is usually mild. Chorea more commonly affects adolescent females. It presents insidiously as moodiness and difficulty in concentrating. Chorea progresses in severity over several weeks until clumsiness, involuntary movements, weakness and ataxia finally suggest the diagnosis. Chorea is frequently a solitary manfestation; fever, carditis and arthritis may not occur. As a result, the diagnosis of acute rheumatic fever may be missed.

RASH

Rash associated with rheumatic fever is now rarely seen except in severe cases. Erythema marginatum is a red, macular, circinate rash on the trunk or proximal extremities (Figure 1). The rash is transient, migratory and nonpruritic. It blanches on pressure, is brought out by fever or the application of heat and is never seen on the face. Erythema marginatum may easily be missed on dark-skinned patients and is reported less frequently in these patients.

SUBCUTANEOUS NODULES

Subcutaneous nodules are also less frequently seen now than they were 40 years ago. [18] These are found over the extensor surfaces of the elbow, knee, wrist and, occasionally, other joints, over the spinous processes of the vertebrae and in the occipital region (Figure 2). The nodules are painless and freely movable under the skin. They often appear in a symmetric pattern and vary in size from 2 to 10 mm.

MINOR CRITERIA

Fever higher than 38 [degrees] C (100.4 [degrees] F) occurs in nearly every patient with acute rheumatic fever, except those patients who have pure chorea or late-onset carditis. Any fever that is unresponsive to aspirin suggests the need to reconsider the diagnosis.

Arthralgia is a minor criterion only in the absence of arthritis; the two together cannot be counted toward fulfilling the Jones criteria.

Multiple serologic tests for evidence of recent streptococcal infection increase the likelihood of detecting acute rheumatic fever, but no single test is positive in all cases. Foe example, aspirin, corticosteriod therapy and congestive heart failure can lower an erythrocyte sedimentation rate that might otherwise be elevated by acute rheumatic fever.

Common electrocardiographic changes include sinus tachycardia, prolongation of the PR interval (first-degree block) and the Wenckeback phenomenon (second-degree, or type, I, block). These abnormalities may be transient or permanent, and frequent ECG monitoring is advisable. A prolonged PR interval is not irrefutable proof of active carditis; it may reflect a previous attack of acute rheumatic fever.

Other common symptoms that are not included in the Jones criteria are fatigue, irritability, weight loss, epistaxis and mild anemia. Abdominal pain severe enough to simulate appendicitis has been reported, [20] as has pneumonitis. Mild renal involvement (51 to 65 percent of patients) [19-20] and liver involvement (64 percent of patients) [19] are also observed.

The least specific combination of signs and symptoms that meet the revised Jones criteria is polyarthritis accompanied by fever and an elevated erythrocyte sedimentation rate; these findings can also fit many other diagnoses. Caution is indicated before diagnosing acute rheumatic fever based on these criteria or on minor clinical manifestations and positive laboratory test results alone.

The World Health Organization has added to the Jones criteria three additional conditions that can point to the diagnosis of acute rheumatic fever (Table 1). In considering the diagnosis of recurrent acute rheumatic fever, it is helpful to remember that subsequent attacks of acute rheumatic fever often have the same constellation of symptoms as the initial attack. Because serologic and culture evidence of recent streptococcal infection can disappear prior to the onset of chorea or delayed carditis, laboratory confirmation is not necessary for the diagnosis of acute rheumatic fever in patients who have a previous history of the disease.

Despite use of the Jones criteria, over-diagnosis of acute rheumatic fever is common (30 to 50 percent in most series). [22,23] Overdiagnosis is certainly less dangerous than underdiagnosis, which leaves the patient without antibiotic prophylaxis and at risk for recurrence.

Pathogenesis

The pathogenesis of acute rheumatic fever remains elusive. [24,26] The resurgence of this disease has been attributed to the reappearance of a more virulent "rheumatogenic" mucoid strain of streptococcus. [27] The rheumatogenic property, if it exists, has not been identified.

Primary Prevention

Because the diagnosis of streptococcal pharyngitis cannot be based solely on clinical examination, throat culture should be performed in patients with sore throats who are at high risk for acute rheumatic fever, including children four to 17 years of age, patients who have had a previous attack of acute rheumatic fever and close contacts of patients with a history of acute rheumatic fever. Only patients who have a positive culture or rapid antigen test should be treated. Antigen detection tests may not be sufficiently sensitive for the diagnosis of streptococcal pharyngitis, [27-28] and we feel a culture should be performed if a negative antigen agglutination detection test is reported. Post-therapy throat cultures are necessary only when the risk of rheumatic fever is high.

The guidelines outlined are tempered by the recognition that many, if not most, patients do not seek medical evaluation for a sore throat, and from one-third to three-quarters of patients with proven acute rheumatic fever cannot recall a recent episode of pharyngitis. [29] Thus, acute rheumatic fever will never be eradicated by primary prevention alone.

In a study conducted more than 40 years ago, [30] penicillin was shown to reduce the incidence of acute rheumatic fever in military recruits. Attempts to reproduce these results have been unsuccessful, and the effectiveness of antibiotics in primary prevention remains unclear. [27] Effective treatment of streptococcal pharyngitis requires adequate antibiotic levels for 10 days. [3]

Treatment failure is managed individually, taking into account noncompliance, reinfection, colonization and possible antibiotic inactivation by beta-lactamase-producing bacterial flora in the oropharynx. Antibiotic inactivation has been reviewed recently in American Family Physician. [32]

Secondary Prevention

From 10 to 30 percent of unprotected individuals who have one episode of acute rheumatic fever experience recurrent attacks. While antibiotic prophylaxis can reduce this rate, controversy exists over the frequency and duration of prophylactic therapy.

Authorities agree that intramuscular benzathine penicillin G best prevents recurrence and promotes compliance, although alternative drugs can be used [32] (Tables 3). Compliance with oral antibiotic prophylaxis may be poor, which makes

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the recurrence rate higher. [22] The American Heart Association recommends an injection every four weeks, and WHO advises a monthly interval for repository penicillin. [17] Since protective levels of penicillin fall three weeks after an injection [33] and a three-week dosing interval has been demonstrated to be more effective in preventing recurrent attacks, [34] both groups advise a three-week interval for high-risk patients.[17,35]

Recurrences of acute rheumatic fever are more likely in children and less likely after puberty. Carditis more commonly recurs in patients with a history of carditis than in patients with a history of chorea; thus, prophylaxis should be continued for a longer period in patients with carditis.

The risk of a second attack of acute rheumatic fever diminshes with time. The risk of recurrence is also related to overcrowding in the patient's environment and exposure to rheumatogenic strains of streptococci.

Prophylaxis should continue for at least five years after the last attack of acute rheumatic fever or through puberty and into the patient's early 20s, perhaps for life. The duration of prophylaxis should be tailored to the patient's disease. [35] Patients who have had rheumatic carditis run a constant risk of recurrent bouts of acute rheumatic fever in adulthood, [19] especially in high-risk situations. For example, a 28-year-old Peace Corps primary school teacher with rheumatic heart disease who is li9ving in Africa remains at high risk, as does a 30-year-old mother sharing a crowded inner-city apartment with her six children.

Prophylaxis for bacterial endocarditis prior to dental or surgical procedures is vital in patients with evidence of rheumatic heart disease. [35] Preprocedure prophylactic therapy should be given in addition to routine acute rheumatic fever prophylaxis.

It is prudent to eliminate the streptococcal carrier state in close contacts of patients with rheumatic heart disease and to watch for the entry of streptococcal infection into households with a history of acute rheumatic fever. This requires routine culture of patients and their families. Children who have an attack of post-streptococcal arthritis should receive penicillin prophylaxis, because they are also at risk of recurrence of arthritis and, perhaps, acute rheumatic fever. [36] Neither the duration nor the effectiveness of prophylaxis has been established.

Treatment

Treatment of acute rheumatic fever should match the manifestations and severity of the attack. Above all, a secure diagnosis is essential before aspirin or corticosteroids are administered. These potent anti-inflammatory agents can mask another diagnosis, such as septic arthritis.

Salicylates obliterate arthritis related to acute rheumatic fever in 24 to 36 hours. Absence of a rapid response to salicylates suggests a different diagnosis. Aspirin is given in divided doses at 100 mg per kg per day in adults. The therapeutic plasma level is 25 to 30 mg per dL.

Corticosteroid therapy should be reserved for patients with severe carditis. Standard doses of prednisone are used; 1 mg per kg per day will usually suffice. Once the disease is controlled, the drug may be slowly tapered over two to three weeks. Aspirin may be continued with corticosteroids, but fluid retention may be a problem.

Rheumatic activity may reappear two to five weeks after the discontinuation of suppressive therapy, and anti-inflamatory drugs may have to be reinstituted. C-reactive protein is the first serologic marker to return to normal during the resolution of the acute phase. Once normalized, C-reactive protein should be monitored periodically for six to eight weeks. Bed rest is advised until the C-reactive protein has been normal for at least two weeks. Supportive management of carditis includes inotropic agents, diuretics, vasodilators and, occasionally, corticosteroids. Chorea is best treated in a quiet environment with sedatives and minor tranquilizers, as required.

Prognosis

Acute rheumativ fever is rarely fatal. Recent published articles in the United States reported only one fatality in 403 cases. [3,4,6-8,10-12] Arthritic symptoms and chorea subside over several months. Mortality and permanent effects from acute rheumatic fever are due to cardiac involvement. A recent longitudinal study found residual rheumatic heart disease in more than one-half of children who had an episode of acute rheumatic fever carditis. [3]

It is difficult to predict the disease course of acute rheumatic fever. Cardiac mumurs may fade and reappear, murmurs may develop in nearly one-half of children with chorea, and optimism from a dramatic response to anti-inflammatory drugs may be tempered. The unpredictable course of acute rheumatic fever requires careful and frequent observation. Prognosis depends on the prevention of repeated attacks and cumulative valve damage.

Final Comment

Acute rheumatic fever can be difficult to identify. The correct diagnosis can only be made after careful review of the history, signs and symptoms, and consultation with physicians familiar with the manifestations of the disease.

References

[1] Markowitz M. The decline of rheumatic fever; role of medical intervention. J Pediatr 1985;106:545-50.

[2] Gillum RF. Trends in acute rheumatic fever and chronic rheumatic heart disease: a national perspective [Editorial]. Am Heart J 1986;111:430-2.

[3] Griffiths SP, Gersony WM. Acute rheumatic fever in New York City (1969 to 1988): a comparative study of two decades. J Pediatr 1990;116:882-7.

[4] Acute rheumatic fever at a Navy training center--San Diego, California. MMWR 1988;37:101-4.

[5] Acute rheumatic fever--Utah. MMWR 1987;36:108-10,115.

[6] Veasy LG, Wiedmeier SE, Orsmond GS, et al. Resurgence of acute rheumatic fever in the intermountain area of the United States. N Engl J Med 1987;316:421-7.

[7] Congeni B. Rizzo C, Congeni J, Sreenivasan VV. Outbreak of acute rheumatic fever in northeast Ohio. J Pediatr 1987;111:176-9.

[8] Hosier DM, Craenen JM, Teske DW, Wheller JJ. Resurgence of acute rheumatic fever. Am J Dis Child 1987;141:730-3.

[9] Bisno AL. The resurgence of acute rheumatic fever in the United States. Annu Rev Med 1990;41:319-29.

[10] Westlake RM, Graham TP, Edwards KM. An outbreak of acute rheumatic fever in Tennessee. Pediatr Infect Dis J 1990;9:97-100.

[11] Wald ER, Dashefsky B, Feidt C, Chiponis D, Byers C. Acute rheumatic fever in western Pennsylvania and the tristate area. Pediatrics 1987;80:371-4.

[12] Chun LT, Reddy DV, Yanamotto LG. Rheumatic fever in children and adolescents in Hawaii. Pediatrics 1987;79:549-52.

[13] Acute rheumatic fever among Army trainees--Fort Leonard Wood, Missouri, 1987-1988. MMWR 1988;37:519-22.

[14] Bisno AL, Shulman ST, Dajani AS. The rise and fall (and rise?) of rheumatic fever. JAMA 1988;259:728-9.

[15] Kaplan EL, Hill HR. Return of rheumatic fever; consequences, implications, and needs. J Pediatr 1987;111:244-6.

[16] Jones Criteria (revised) for guidance in the diagnosis of rheumatic fever. Circulation 1984;69:204A-8A.

[17] Rheumatic fever and rheumatic heart disease. Report of a WHO Study Group. WHO Tech Rep series 1988;764:1-58.

[18] Rheumatic Fever Working Party of the Medical Research Council of Great Britain and the Subcommittee of Principal Investigators of the American Council on Rheumatic Fever and Congenital Heart Disease, American Heart Association. The treatment of acute rheumatic fever in children. A cooperative clinical trial of ACTH, cortisone, and aspirin. Circulation 1955;11:343-77.

[19] Barnert AL, Terry EE, Persellin RH. Acute rheumatic fever in adults. JAMA 1975;232:925-8.

[20] Lin JS, Rodriguez-Torres R. Appendectomy in children with acute rheumatic fever. Pediatrics 1969;43:573-7.

[21] Cohen S, Solomon M, Grishman E, Gribetz D, Churg J. The kidney in acute rheumatic fever. Clinicopathological correlations. Arch Intern Med 1971;127:245-9.

[22] Flight RJ. The Northland rheumatic fever register. NZ Med J 1984;97:671-3.

[23] Rice MJ, Kaplan EL. Rheumatic fever in Minnesota. II. Evaluation of hospitalized patients and utilization of a State Rheumatic Fever Registry. Am J Public Health 1979;69:767-71.

[24] Cairns LM. The immunology of rheumatic fever. NZMED J 1988;101(847 Pt 2):388-91.

[25] Zabriskie JB. Rheumatic fever: a model for the pathological consequences of microbial-host mimicry. Clin Exp Rheumatol 1986;4:65-73.

[26] Bisno AL. Group A streptococcal infections and acute rheumatic fever. N Engl J Med 1991;325:783-93.

[27] Hutten-Czapski P. Management of streptococcal pharyngitis: the conundrum of acute rheumatic fever. Fam Pract 1988;5:200-8.

[28] Kaplan EL. Rapid detection of group A stretococcal antigen for the clinician and the epidemiologist: accurate? cost-effective? useful NZ MED J 1988;101(847 Pt 2):401-2.

[29] Gray GC, Escamilla J, Hyarns KC, Struewing JP, Kaplan EL, Tupponce AK. Hyperendemic Streptococcus pyogenes infection despite prophylaxis with penicillin G beanzathine. N Engl J Med 1991;325:92-7.

[30] Gerber MA, Randolph MF, Chanatry J, Wright LL, DeMeo KK, Anderson LR. Antigen detection test for streptococcal pharyngitis: evaluation of sensitivity with respect to true infections. J Pediatr 1986;108(5 Pt 1);654-8.

[31] Schwartz RH, Wientzen RL Jr, Pedreira F, Feroli EJ, Mella GW, Guandolo VL. Penicillin V for group A streptococcal pharyngotonsillitis. A randomized trial of seven vs ten days' therapy. JAMA 1981;246:1790-5.

[32] Pichichero ME. Controversies in the treatment of streptococcal pharingitis. Am Fam Physician 1990;42:1567-76.

[33] Kaplan EL, Berrios X, Speth J, Siefferman T, Guzman B, Quesny F. Pharmacokinetics of benzathine penicillin G: serum levels during the 28 days after the intramuscular injection of 1,200,000 units. J Pediatr 1989;115:146-50.

[34] Lue HC, Wu MH, Hsieh KH, Lin GJ, Hsieh RP, Chiou JF. Rheumatic fever recurrences: controlled study of 3-week versus 4-week benzathine penicillin prevention programs. J Pediatr 1986;108:229-304.

[35] Danjani AS, Bisno Al, Chung KJ, et al. Prevention of rheumatic fever. A statement for health professionals by the Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease of the Council on Cardiovascular Disease in the Young, the American Heart Association. Circulation 1988;78:1082-6.

[36] De Cunto CL, Giannini EH, Fink CW, Brewer EJ, Person DA. Prognois of children with poststreptococcal reactive arthritis. Pediatr Infect Dis J 1988;7:683-6.

WILLIAM A. ALTO, M.D. is associate director of the St. Mary's Hospital Family Practice Residency Program, Grand Junction, Colo. A graduate of the University of Rochester (N.Y.) School of Medicine, Dr. Alto completed a family practice residency at the University of Massachusetts, Worcester.

ROBERT GIBSON, M.D. has a private family practice in Palisade, Colo. Dr. Gibson is a graduate of the University of Mississippi School of Medicine, Jackson, and completed a residency at the St. Mary's Family Practice Residency Program.

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