Demam Rematik Akut

01Pathophysiology

Acute rheumatic fever (ARF) is a non-suppurative, delayed autoimmune complication of pharyngeal infection by Group A Streptococcus (GAS), Streptococcus pyogenes. It is not caused by direct bacterial invasion of the heart or joints. Instead, the disease arises from a misdirected immune response that occurs 1 to 5 weeks after the initial pharyngitis episode.

The central mechanism is molecular mimicry. GAS surface proteins, particularly the M protein, share structural homology with human cardiac myosin, laminin, tropomyosin, and neuronal tissue (basal ganglia). Following pharyngeal infection, the host mounts an antibody and T-cell response against streptococcal antigens. Because of the antigenic cross-reactivity, these immune effectors also target the host's own tissues, resulting in inflammation at several anatomical sites.

Carditis (30-82% of cases) is the hallmark and the most prognostically important manifestation. The inflammatory process targets the endocardium (valvulitis), myocardium, and pericardium. Valvulitis preferentially affects the mitral valve, followed by the aortic valve. The autoimmune assault causes leaflet edema, chordal thickening, and eventually regurgitation. This is why a new-onset pansystolic murmur at the apex (mitral regurgitation) or an early diastolic murmur along the left sternal border (aortic regurgitation) is usually heard. Approximately 50% of patients with carditis will progress to permanent valvular scarring (rheumatic heart disease), making carditis the primary determinant of long-term prognosis.

Arthritis (70-80% of cases) is the most common presenting complaint. The inflammatory mediators deposit in the synovium of large joints, producing the classic migratory polyarthritis. The reason the pain "migrates" is that inflammation in one joint is self-limiting (resolving in days), while new joints become involved sequentially.

Sydenham chorea (10-30%) results from autoantibodies targeting the basal ganglia neurons. The latency for chorea can be longer than for other manifestations, up to 6-8 months, which is why chorea can present as a standalone criterion without concurrent evidence of streptococcal infection.

Erythema marginatum and subcutaneous nodules are rare cutaneous manifestations. Erythema marginatum represents a vasculitic process in the dermal vessels, producing the characteristic serpiginous, non-pruritic, evanescent rash on the trunk and proximal extremities. Subcutaneous nodules consist of perivascular collections of inflammatory cells (resembling Aschoff bodies) located over bony prominences (elbows, knees, wrists, occiput, spinous processes).

A key concept for examination purposes: the disease follows a recurrence-dependent progressive model. Without secondary prophylaxis, each new exposure to a different GAS strain can trigger a new ARF episode, and each episode causes cumulative, worsening valve damage. The risk of recurrence is highest in the first year after the initial attack. This is why lifelong or long-term secondary prophylaxis with BPG is non-negotiable.

02Clinical Manifestation & Classification

The revised 2015 Jones Criteria (AHA) stratify diagnostic criteria based on population risk. Indonesia is classified as a moderate-to-high risk population. This distinction is critical because the threshold for certain criteria differs between groups.

Jones Criteria by Population Risk

First, in a moderate-to-high risk population, monoarthritis qualifies as a major criterion, whereas in low-risk populations only polyarthritis counts as major. A vignette describing a single swollen, hot knee in a child from an endemic area should still raise your index of suspicion for ARF. Second, the fever threshold is lower (38.0 C vs 38.5 C) and the ESR cutoff is lower (30 vs 60 mm/hr) in the moderate-to-high risk group, making these criteria deliberately more sensitive to avoid missed diagnoses at the cost of reduced specificity.

Diagnostic Combinations Required

Joint manifestations cannot be double-counted. If polyarthritis is used as a major criterion, arthralgia cannot simultaneously serve as a minor criterion in the same patient.

Clinical Manifestations

03Diagnostic Workup

Workup Logic in Detail

Step 1: Establish evidence of preceding GAS infection. This is a prerequisite for diagnosis (except for standalone chorea or late-presenting carditis). The Pedoman DRA & PJR PERKI 2026 emphasizes that serologic testing (ASTO and Anti-DNase B) is preferred over culture for confirming a causal link, because by the time ARF manifests (weeks later), the pharyngeal infection has often resolved and cultures may be negative. A positive throat culture alone is not strong enough evidence because carrier rates are high, particularly in children (around 15%). Ideally, an elevation in both ASTO and ADB is more convincing than either alone. A four-fold rise in titer between acute and convalescent sera (12-18 days apart) historically represented the strongest evidence, though modern assay methods (turbidimetry, nephelometry) have not been validated for this threshold.

Be aware that ASTO can also be elevated in Bacillus cereus infection, Pseudomonas infections, scarlet fever (Group C Streptococcus), and toxic shock syndrome (Group G Streptococcus). Therefore, an isolated ASTO elevation does not diagnose ARF without clinical correlation.

Step 2: Assess clinical criteria using the Jones framework. Count how many major and minor criteria the patient fulfills. In moderate-to-high risk populations like Indonesia, monoarthritis and subclinical carditis are accepted as major criteria, broadening the diagnostic sensitivity.

Step 3: Echocardiography is mandatory. Pedoman DRA & PJR PERKI 2026 states that echocardiography is far more sensitive and specific than auscultation alone for detecting carditis and is therefore obligatory for all patients with suspected or confirmed ARF. Subclinical carditis (valvulitis detected on echo without an audible murmur) is now accepted as a major criterion in both risk groups. The WHF echocardiographic criteria for pathologic mitral regurgitation require all four of: visible in 2 views, jet length >2 cm (or >1.5 cm if body weight <30 kg), velocity >3 m/s for one complete envelope, and pansystolic jet in at least one envelope.

Step 4: Exclude mimics. Before finalizing the diagnosis, rule out congenital heart disease (bicuspid aortic valve, congenital mitral anomalies), septic arthritis, juvenile idiopathic arthritis (JIA), and systemic lupus erythematosus (SLE).

The Best Initial Test in a child with suspected ARF after a recent sore throat is: order ASTO + Anti-DNase B + ESR + CRP + ECG, and refer for echocardiography. The Most Accurate / Confirmatory Test for cardiac involvement is transthoracic echocardiography using Doppler imaging (Pedoman DRA & PJR PERKI 2026).

04Management & Treatment

Acute Stabilization

The immediate priority upon suspecting ARF is twofold: eradicate GAS and control symptoms.

First, administer eradication therapy with BPG intramuscularly (single dose: 600,000 IU for patients ≤20 kg; 1,200,000 IU for patients >20 kg). The intramuscular route is preferred because it guarantees compliance and achieves therapeutic levels reliably. Oral alternatives (Phenoxymethylpenicillin 15 mg/kg BID for 10 days, or Amoxicillin 50 mg/kg once daily for 10 days) are acceptable when IM injection is not possible (Pedoman DRA & PJR PERKI 2026, Tabel 3.3). For penicillin-allergic patients: Azithromycin 12 mg/kg/day for 5 days, Erythromycin ethyl succinate 20 mg/kg BID for 10 days, Clindamycin 7-10 mg/kg TID for 10 days, or Cephalexin 25 mg/kg BID for 10 days (for non-anaphylactic allergy only).

Second, manage inflammation. A critical clinical pearl: avoid NSAIDs until the diagnosis is confirmed. Premature NSAID use masks the migratory pattern of arthritis and suppresses fever, potentially causing the patient to no longer meet Jones Criteria. Use paracetamol only for pain relief during the diagnostic workup period.

Arthritis without carditis: Once diagnosis is confirmed, start naproxen (10-20 mg/kg/day divided BID, max 1,250 mg/day) as first-line. Ibuprofen (5-10 mg/kg/dose TID, max 2,400 mg/day) is an acceptable alternative. Aspirin (50-60 mg/kg/day in 4-5 divided doses, can increase to 80-100 mg/kg/day) is second-line due to the risk of Reye syndrome in children. NSAIDs should be tapered after 1-2 weeks based on clinical response and normalization of inflammatory markers.

Carditis: For severe carditis or carditis with heart failure, prednisone 1-2 mg/kg/day (max 80 mg/day) is recommended, given once daily or in divided doses. Treat for 1 week, then taper by 20-25% per week, for a total duration generally not exceeding 3 weeks. When corticosteroids are started, NSAIDs can be discontinued because steroids are more effective at controlling all ARF manifestations. Standard heart failure therapy (diuretics, ACE inhibitors) is given concurrently.

Before initiating immunosuppressive-dose corticosteroids (prednisolone ≥10 mg/day for ≥4 weeks in adults, or >0.5 mg/kg/day for ≥2 weeks in children), screening for latent infections is required: tuberculosis (IGRA or Mantoux), hepatitis B (HBsAg, HBcAb, HBsAb), hepatitis C, HIV, melioidosis, strongyloidiasis, and scabies.

Chorea: Mild cases may not require pharmacologic treatment. Moderate-to-severe chorea is treated with carbamazepine (3.5-10 mg/kg BID) or sodium valproate (7.5-10 mg/kg BID). For very severe or paralytic chorea, add prednisolone.

BPG injection technique: The Pedoman DRA & PJR PERKI 2026 describes a lidocaine co-injection technique to reduce pain. Draw the BPG into a new 3 mL syringe, then draw 0.5 mL of 1% lidocaine (or 0.25 mL of 2% lidocaine) into the tip of the same syringe without mixing so that lidocaine is injected first. Administer deep IM into the ventrogluteal site or vastus lateralis, slowly over at least 2-3 minutes. Never administer IV.

Secondary Prophylaxis

The regimen of choice is BPG 1,200,000 IU IM every 28 days (every 21 days for select high-risk individuals). If IM is absolutely not possible, oral Phenoxymethylpenicillin 250 mg BID is the oral alternative. For patients with severe penicillin allergy, erythromycin 250 mg BID is used.

Patients already on secondary prophylaxis who develop a new episode of acute pharyngitis should still receive a full course of oral antibiotics (e.g., amoxicillin for 10 days), especially if the last BPG injection was more than 7 days prior, because penicillin levels become subtherapeutic in the 3rd-4th week after injection.

05Differential Diagnosis & Distractors

06Traps & High-Yield Pearls

The single most common way students lose points on ARF questions is confusing the role of ASTO with the diagnosis itself. An elevated ASTO does not diagnose ARF. It only provides evidence of a preceding GAS infection. The diagnosis of ARF is clinical, made via the Jones Criteria. Conversely, a normal ASTO does not rule out ARF if Anti-DNase B is elevated, or if the patient presents with standalone chorea (which has a latency of up to 6-8 months, by which time ASTO may have normalized).

The second major trap involves premature NSAID use. A vignette may describe a child with joint pain and fever who is started on ibuprofen by a well-meaning physician. The arthritis resolves, the fever breaks, and now the child no longer meets enough Jones Criteria for diagnosis. The teaching point: use paracetamol only until ARF is confirmed or excluded. Starting NSAIDs too early obscures the migratory pattern and suppresses the fever, both of which are diagnostically critical (Pedoman DRA & PJR PERKI 2026, Bab V, Sec. 5.2).

The third common pitfall involves monoarthritis in an endemic population. In a low-risk population, monoarthritis is not a major Jones criterion. But in a moderate-to-high risk population (such as Indonesia), monoarthritis qualifies as major. A question set in a developing country showing a child with a single swollen knee, fever, elevated ASTO, and elevated ESR should prompt you to consider ARF, not dismiss it because "polyarthritis is required."

Fourth, students often forget that subclinical carditis (detected only on echocardiography, with no audible murmur) is now a major criterion in both risk groups. A vignette describing a child who meets one clinical major criterion (e.g., arthritis) and one minor criterion (e.g., fever), and whose echo reveals pathologic mitral regurgitation despite a clean auscultation, now meets 2 major criteria and has confirmed ARF. This is why echocardiography is mandatory for all suspected cases, not optional (Pedoman DRA & PJR PERKI 2026, Bab II, Sec. 2.5).

Fifth, regarding management: corticosteroids for ARF carditis do not prevent progression to RHD. They control acute inflammation and symptoms (fever, pericarditis, heart failure), but no anti-inflammatory therapy has been proven to alter the long-term natural history of valve scarring. The only intervention proven to prevent RHD progression is secondary prophylaxis with BPG by preventing recurrent ARF episodes that cause cumulative valve damage.

The core competency being tested across all ARF questions is threefold: recognizing the disease from its clinical pattern (migratory large-joint arthritis after pharyngitis in a school-age child from an endemic area), applying the correct Jones Criteria tier based on population risk, and understanding that the definitive intervention is not the anti-inflammatory but the lifelong prophylactic BPG that breaks the cycle of recurrence.